Dr. Kevin Beaver the Apostle

In the discussion following my previous video about monoamine oxidase A, I noted a new study with lead author Dr. Kevin Beaver. The study closely resembles his previous study of the 2-repeat allele, my analysis of which is well on its way to becoming my most popular blog essay. Once again, a small subset of African-American men from the National Longitudinal Study of Adolescent Health served as a comparison group for the eight African-American men, who possess this rare allele of the upstream promoter for MAOA and who had complete phenotype data. This time, the specific behaviors of shooting or stabbing replaced measures of psychopathic personality, arrests, and incarceration as the outcomes of interest. Despite the small sample size, the results were significant (odds ratio = 12.89, p < 0.05) because those with the allele had a fifty-percent chance of shooting or stabbing someone. For African-American men without this allele, the risk was only seven percent. Those with MAOA-2R were also more likely to have victimized multiple people based on their greater likelihood of admitting stabbing or shooting during multiple “waves” of study follow-up.

I still have concerns about population substructure. In a mixed population like African Americans, alleles associated with African ancestry like MAOA-2R might correlate with many other African alleles, and because MAOA-2R is so much more common in African Americans than whites and Asians, scientists have studied no other sample and no other race for behavioral phenotypes specifically for this allele. However, Guo et al previously demonstrated the functional differences between MAOA-2R and the other alleles in vitro.

This study bares the imprint of my influence. I previously sent Beaver a list of questions that reflected beliefs of mine about the research on this gene. Here was one such question:

In your studies of MAOA, you used the convention of including the 2-repeat and 3-repeat alleles in the category MAOA-L, but Guo et al “The integration of genetic propensities into social-control models of delinquency and violence among male youths” and Guo et al “The VNTR 2 repeat in MAOA and delinquent behavior in adolescence and young adulthood: associations and MAOA promoter activity” found that the 2-repeat allele had twice as much effect on violent delinquency as either the 3-repeat or 4-repeat alleles and that the 2-repeat allele had more effect than the dopamine genes DAT1 and DRD2. How do you justify following the MAOA-L convention rather than studying the 2-repeat allele separately?

In this study, Beaver et al make the following similar remark:

[A]lmost all of the prior research examining the effects of MAOA on antisocial behaviors has pooled the 2-repeat allele together with the 3-repeat allele. As the results of this study indicate, however, this approach may be misguided as the most powerful effects may be found within the 2-repeat allele and combining the 2-repeat allele with the 3-repeat allele may attenuate the main effects of MAOA.

I raised another concern in a separate question:

A disproportionate number of studies on MAOA and antisocial personality disorder were negative (Saito et al, Koller et al, Parsian et al, Lu et al, and Prichard et al). Why should antisocial personality disorder be a focus of genetic research? Should not the aggression or impulsive criteria of antisocial personality disorder be considered separately in genetic studies?

Beaver et al echo my concern:

Using an additive scale of antisocial behaviors may mask important heterogeneity that exists between the individual behaviors and MAOA genotype such that MAOA may be related to certain types of antisocial behaviors, but not others. As a result, to further unpack the nexus between MAOA genotype and serious violence, the current study examines only extreme violence as measured by shooting and stabbing behaviors.

Neuroskeptic, who has been a reader of the Unsilenced Science, responded to the study by saying, “Hmmm,” to which neurogeneticist Dr. Kevin Mitchell responded, “Grrrrr,” undoubtedly while pounding his chest. University of North Carolina geneticist Dr. Patrick Sullivan wrote, “I would have rejected wo review. Studies like these have not taught us much.” By “studies like these,” I assume he means the hundreds of corroborating studies pertaining to the MAOA gene, its enzyme, and its metabolites, but dismissive flippancy from genetics professors is the sign of the times. Mitchell passed along my recent video to his fellow GWAS Jihadists “based on the title,” which is clearly a Christmas miracle. I, for one, generally do not consider candidate-gene studies with large effect sizes to be evidence of no effect at all “by historical analogy.” In the past, interesting studies would lead to attempts to replicate the finding. Often some attempts would support, others would not, and a meta-analysis of all pertinent results would provide the final word. Now, some attempts support, and every attempt that does not support the original finding is evidence of a broader dysfunction in medicine or science, which are to blame for the media’s hype. Only a select few GWAS Jihadists have the moral courage to dismiss every positive finding with a self-righteous fist pound on the lectern. Nevertheless, Vimaleswaran et al determined that candidate-gene studies, which follow hypotheses about specific genes, show “evidence for enrichment” when compared to genome-wide association studies (for obesity) such that “the candidate gene approach retains some value.” Tielbeek et al attempted to test MAOA in a GWAS that only examined single nucleotide polymorphisms and found no effects for antisocial behavior. Of course, such a study could not directly examine the VNTR promoters that have drawn so much interest to this gene.

Eight is a small number of cases, but it is approximately the same as the number of cases of Brunner syndrome when that diagnosis was established in 1993, a diagnosis that only recently came into use for two additional families. When I first confronted the GWAS Jihadists, I asked them if their disbelief in the gene-environment interaction for MAOA-3R extended to a disbelief in Brunner syndrome. They defensively denied reaching that conclusion. The lesson is obvious: in order to establish the effect of MAOA-2R on violence as a trustworthy scientific finding, this allele’s effect must have an eponym. But which scientist should the disease immortalize? Will it be Guo syndrome or Beaver syndrome? (How about nooffensebut syndrome?) We could follow the example of entomologists, Quentin Wheeler and Kelly Miller, and name this after the greatest president of my lifetime: George W. Bush syndrome. However, as any graduate of medical school can attest, eponyms are evil. The study of genetics as it pertains to social sciences might gain the respectability of physics if it follows physics naming conventions. Just as flavors of quarks have creative names like strange and charm, the disease with symptoms of shooting people and stabbing people caused by the allele MAOA-2R should be called sunshine syndrome.










Beaver KM, Barnes JC, & Boutwell BB (2013). The 2-Repeat Allele of the MAOA Gene Confers an Increased Risk for Shooting and Stabbing Behaviors. The Psychiatric quarterly PMID: 24326626

Piton A, Redin C, & Mandel JL (2013). XLID-causing mutations and associated genes challenged in light of data from large-scale human exome sequencing. American journal of human genetics, 93 (2), 368-83 PMID: 23871722

Tielbeek JJ, Medland SE, Benyamin B, Byrne EM, Heath AC, Madden PA, Martin NG, Wray NR, & Verweij KJ (2012). Unraveling the genetic etiology of adult antisocial behavior: a genome-wide association study. PloS one, 7 (10) PMID: 23077488

Vimaleswaran KS, Tachmazidou I, Zhao JH, Hirschhorn JN, Dudbridge F, & Loos RJ (2012). Candidate genes for obesity-susceptibility show enriched association within a large genome-wide association study for BMI. Human molecular genetics, 21 (20), 4537-42 PMID: 22791748

The Stupid Stupidity Surrounding the Warrior Gene, MAOA, is Stupid

Byrd AL, & Manuck SB (2013). MAOA, Childhood Maltreatment, and Antisocial Behavior: Meta-analysis of a Gene-Environment Interaction. Biological psychiatry PMID: 23786983

Black Suits, Gowns, & Skin: SAT Scores by Income, Education, & Race

People with highly educated or wealthy parents score higher on the SAT than those from poor, uneducated families. Obvious statistic is obvious, but how important are dollars and degrees compared to race? The College Board, the organization that oversees the SAT, holds tight to its information on the subject, but incomplete leaks have occurred for 1995, 1997, 2003, and 2008. 1995’s top income bracket only started at $70,000, so the wealthiest African-American students that year did not outscore even the poorest white students. As shocking as that fact is, it provides no controls for confounding variables and neglects the currently largest minority, Hispanic Americans. Therefore, I decided to approach the question using multiple linear regression of state data. ("M" in the graph below stands for the math subtest. "V" stands for the critical reading or verbal subtest.)

First, I shall review the important news from this year’s SAT and ACT score reports. I used the ACT-to-SAT conversion equation that I extracted from the conversion table to construct a summary graph of overall ACT-SAT scores for each race and gender. Asian scores continued to rise, despite the College Board’s South Korean crackdown, which was based upon suspicions of widespread cheating. Meanwhile, overall scores fell, and whites, Native Americans, and men declined this year more than any of the previous sixteen available years.

Native Americans now barely score higher than Hispanic Americans. Native-American ACT scores slipped especially fast, and their average score on the optional ACT writing exam now equals those of African Americans. Since many white people have Native-American ancestry, and Canadian and US Native Americans tend to have high amounts of European ancestry, Native-American score trends could reflect changing cultural attitudes about racial identification, but their absolute number of test participants has not changed greatly.

I previously commented on evidence for possible white decline. So far, the evidence is subtle. If future scores demonstrate long-term decline, it could signify the “dumbing down” of education or culture, dysgenics, minority-centered education reforms, or low rates of whites taking test preparation services.

Because Asian score increases have been steady and measured, I believe that these represent genuine progress, even with or perhaps due to the same root causes as the reported cheating scandals among Asians. However, I suspect that Asian progress will eventually level off because most racial score gaps have stayed remarkably constant, and I think nature influences testing potential, especially among those of adequate means.

SAT annual reports provide scores of students grouped by their parents’ income and education levels. These graphs of that data should not surprise anyone.

The fluctuation of income categories tells an interesting story about the past two decades. The number of people with six-figure incomes took off not that long ago.

Despite the fact that levels of (parents’) education have been trending upwards, coming from an educated family increasingly predicts obtaining a higher SAT score. This graph of educational advantage is a Cohen’s d graph with the vertical axis zoomed in. I defined those parents with a bachelor’s or graduate degree as “educated.” (This graph uses the older term for the critical reading subtest, verbal.)

Parents’ education and income show clear links to SAT scores, but so do many other variables. When I mapped state SAT scores, I discovered that Midwestern states achieved higher scores than other states because a small percentage of studious Midwesterners took the SAT, and most other college-bound students in those states only took the ACT. Simple linear regression of state SAT scores with only participation rate as the predictor variable explains 78 percent of variance (P = 10^-273). Usually psychology research conducts this kind of analysis with a sample population, but I cannot access the College Board’s raw data, obviously. I am trying to reverse-engineer an SAT database with 16 years of state data. However, a single data point for an income category could represent tens of thousands of people or as few as three. Plus, the year could potentially influence scores due to inflation or even societal changes in cognitive abilities, the so-called Flynn effect. I can appropriately control for those variables, but controlling for race would require estimation because racial group proportions are not broken down every year within each income bracket and educational degree. Therefore, I turned income and education levels into continuous variables for multiple linear regression.

For linear regression, I turned income into a continuous variable by dividing the number of students whose parents earn six-figure incomes by the number whose parents earn less than $20,000 per year. I compared results for this income “gap” to an income “divide” based on the number whose parents earn more than $60,000 per year divided by those whose parents earn less. I created a variable for education based on the number whose parents achieved at least a bachelor’s degree divided by the number whose parents did not. The racial variable was the number of whites and Asians divided by the number of another race. Simple linear regression for state population size showed that it was a significant predictor of SAT scores (P=4.3 x 10^-47) that explained 22 percent of variance. However, it became insignificant with all further analysis except when the other predictor variables were either participation, year, and income gap or participation, year, education, and income divide with or without race. Year did not produce a significant P value for simple linear regression (P = 0.5) but always did in multiple linear regression of income or education, lowering scores over time like a reverse-Flynn effect. Both income gap and income divide were significant predictor variables in multiple linear regression, but income divide slightly better predicted SAT scores, explaining 86 percent of variance with year and participation variables, compared to 85 percent for income gap with year, size, and participation variables. Multiple linear regression with participation rate, year, income divide, and education explained 90 percent of variance with all variables achieving statistical significance, but the addition of education caused the P value of the income divide to worsen from 10^-83 to 10^-3. When I added race as an additional variable, the income divide was no longer a significant predictor of SAT scores (P = 0.4). Most of the impact of income on SAT scores stems from its ability to predict parents’ education levels. Multiple linear regression with the remaining significant variables (state sample size, participation rate, year, education, and race) explained 92 percent of SAT variance.

Graphs of actual SAT scores for income brackets and education levels show the distinctiveness of children whose parents have graduate degrees. Trendlines are given with R-squared variances for the highest and lowest categories.

The graphs for income or education with race reach the provocative result that race affects scores more among the lower rungs of society. As the data only represents state racial proportions, the results leave room for debate. For instance, the furthest left data in the graphs below represent Washington, DC, which I actually treated as a state. Higher-income families there are probably more likely to be white or Asian-American than are lower-income families. Many racially diverse states like California have industries or attractions that pull in successful, educated whites. Nevertheless, one could use these results to defend upper-class affirmative-action beneficiaries or to call for a new class-based system to benefit the many poor, but intelligent whites and Asian Americans.

Also of note is the fact that these graphs look totally awesome.










Anonymous (1998). Why Family Income Differences Don't Explain the Racial Gap in SAT Scores The Journal of Blacks in Higher Education (20), 6-8 DOI: 10.2307/2999198

Anonymous (2008). Why Family Income Differences Don't Explain the Racial Gap in SAT Scores The Journal of Blacks in Higher Education (62), 10-12

Ezekiel Dixon-Roman, Howard Everson, & John McArdle (2013). Race, Poverty and SAT Scores: Modeling the Influences of Family Income on Black and White High School Students’ SAT Performance Teachers College Record, 115 (4), 1-33

The SAT-ACT Score Map

(Note: Following this post, I shall focus on finishing the MAOA bibliography probably until it is up-to-date and until I can better quantify its data.)

In my last post on college-entrance exams, I left incomplete the task of properly controlling for test participation a state map of combined SAT and ACT scores. I had already explored group average SAT gaps by race and gender and SAT score distributions. Finally, I am posting above what I consider the definitive state map, which is properly controlled for test type and state participation levels.

The map demonstrates my contention that American demographic changes contribute to a North-South educational divide. Detailed mapping of potential academic decline can help inform discussion of policies like “immigration reform,” help extrapolate future global competitiveness of the American workforce, and delineate regional economic fault lines. In the explanation that follows, I compare the effects of state participation in the SAT and ACT and race with regression analysis. Then, I shall review an important study on the relative importance of these scores and what might augment or replace them.

Testing associations publish a standardized table to convert between ACT and SAT scores. The primary table converts between the composite ACT score and the combined SAT mathematics and critical-reading (formerly verbal) score. (I divided the scores in half for purposes of comparison with SAT subtest scores.) A separate table converts between the newer SAT writing score and the score for the optional ACT writing exam. However, I shall neglect the writing scores data at this time, but the previous post maps raw SAT writing scores.

My last attempt at ACT-to-SAT score conversion amounted to a crude estimate that only accounted for the highest and lowest ACT scores with a line drawn between for all others. The tests follow different scales with several possible SAT scores coinciding with almost all ACT scores. Therefore, I created a new formula based on linear regression of the plot of average SAT scores for each ACT increment. Since state ACT averages tend to hover around 21, this graph illuminates how my previous formula unfairly underestimated states that emphasize the ACT over the SAT.


As states increasingly have required the ACT for all high-school graduates, their average scores have declined. Plotting below each state’s yearly ACT and SAT score since 1998 by participation level confirms the association. All associations achieve statistical significance (P=9.54 x 10^-27 for the ACT, P=3.75 x 10^-33 for the weighted SAT-ACT scores) with the SAT, alone, achieving the greatest significance of any tested relationship in this entire effort (P=5.4 x 10^-245) and the largest coefficient of determination (0.769). Midwestern states that strongly emphasize the ACT achieved impressive average SAT scores and seem to have an outsized impact on this finding. The combined SAT-ACT participation rates are out of a possible 200%, which would require all high-school graduates to take the SAT and the ACT.


The comparison of score maps to demographic trends, which I presented with a map of the percentage of SAT examinees who are white or Asian, fits the familiar national racial group mean gaps. Simple linear regression better quantifies the effect of race, and multiple linear regression can tease apart the effect of state participation levels. Asians have the highest scores, but I lumped whites with Asians because Asians are a relatively small group. I would expect other racial gaps to be too confounding to separate Asians from the rest. The distinction I drew might seem arbitrary, but many institutions separate data on Asians and whites from that of “underrepresented minorities.” The graphs of scores by racial proportion appear to show that these are linear associations, all of which are significant (P=3.51 x 10^-53 for the SAT, P=1.33 x 10^-41 for the ACT, and P=1.48 x 10^-40 for the tests combined). Multiple regression shows that all associations remain significant. For the combined SAT-ACT score, participation had a P-value of 3.35 x 10^-22, and race had a P-value of 1.29 x 10^-29. The multiple regression model set score equal to 986 – 0.782 x participation (as a whole number) + 97.5 x the percentage white or Asian.


The residuals from subtracting this model from the raw data fit a Gaussian distribution, as expected. So, I recalculated the SAT-ACT composite scores by adding the residuals back to the model under the assumption of 100% (out of a possible 200%) participation.


While the score map might not appear identical to the map of demographic trends, one can make out a North-South gradient, and state efforts to adopt test requirements seem well-controlled. Further analysis could use ANCOVA for income categories or compare racial gaps within states. Composite writing scores could prove useful, despite the shorter timeframe for the SAT and the optional nature of the ACT written exam. In fact, the states of Texas, Nevada, and Florida might not seem to perform so badly in this map, given their diversity, but their raw SAT writing scores were especially low. Then again, immigration weighing down English writing skills could resolve with acculturation.

Now, I wish to review a 2009 study on the relative relevance of SAT and ACT scores. Schmitt et al compared the predictive value of those scores to high-school grades and twelve “noncognitive predictors”: knowledge, curiosity, adaptability, perseverance, ethics (“not cheating”), career orientation, healthy behaviors, interpersonal skills, “leadership,” community volunteer activities, “artistic and cultural appreciation,” and “appreciation for diversity” (“e.g. by culture, ethnicity, religion, or gender”). As the US Supreme Court revisits the issue of Affirmative Action in college admissions, universities might apply such predictors to lessen the influence of standardized tests. None of the “noncognitive predictors” could predict college grades even half as well as either high-school grades or the SAT/ACT scores, which had correlations of 0.531 and 0.539, respectively. Knowledge came closest, but I think knowledge is cognitive. Career orientation actually was alone in its statistically significant negative association with college grade-point average. The authors offered as their only explanatory hypothesis the poor performance of African Americans “for whom career mobility and a career orientation was a major reason for college attendance.” Indeed, career orientation was the strongest advantage for African Americans, who barely scored higher than whites on “appreciation for diversity.” Their only other advantage was perseverance. High-school grades underestimated African-American college grades, but not as much as SAT/ACT scores overestimated. Adding the “noncognitive” criteria to potential admissions selection would lower college grades, in general, but raise African-American and Hispanic-American admissions at the 15% most exclusive universities, at the expense of white and especially Asian-American applicants. However, African-American college graduation rates would fall eight percentage points at such institutions. SAT/ACT scores were significantly associated with higher college classroom absenteeism and lower “organizational citizenship behavior,” with which “appreciation for diversity” had a significant positive association. In other words, the more intelligent students were less inclined to go to all lectures, promote “the university to outsiders,” defend “it against criticism,” and participate “in student government or other clubs” to make the university “a better place.” The authors did not conclude that those are relatively unintelligent behaviors.










Schmitt N, Keeney J, Oswald FL, Pleskac TJ, Billington AQ, Sinha R, & Zorzie M (2009). Prediction of 4-year college student performance using cognitive and noncognitive predictors and the impact on demographic status of admitted students. The Journal of applied psychology, 94 (6), 1479-97 PMID: 19916657

Why YouTube Sucks Episode II – The Phantom Menace

I must apologize for taking a break from expanding the MAOA bibliography to interject myself into a YouTube debate about heredity.

Monoamine Oxidase A Bibliography

Last updated: 1-16-2015

Bookmark this as a resource for research related to monoamine oxidase A (MAOA) or “the warrior gene.” New studies will appear as they become available. If a study is missing that belongs here, please email n00ffensebut@gmail.com. Also, be sure to read my own detailed analyses.

MAOA Allele Frequencies

	2R	2.5R	3R	3.5R	4R	5R	6R
All Raw	108	2	8769	173	11437	175	0
All %	0.5226%	0.0097%	42.4361%	0.8372%	55.3475%	0.8469%	0.0000%
White Raw	26	2	4618	164	8032	146	0
White %	0.2002%	0.0154%	35.5559%	1.2627%	61.8417%	1.1241%	0.0000%
Black Raw	46	0	542	3	448	9	0
Black %	4.3893%	0.0000%	51.7176%	0.2863%	42.7481%	0.8588%	0.0000%
Asian Raw	19	0	2433	1	1559	2	0
Asian %	0.4733%	0.0000%	60.6129%	0.0249%	38.8391%	0.0498%	0.0000%
Hispanic Raw	0	0	27	0	65	0	0
Hispanic %	0.0000%	0.0000%	29.3478%	0.0000%	70.6522%	0.0000%	0.0000%
Native Raw	0	0	220	1	354	2	0
Native %	0.0000%	0.0000%	38.1282%	0.1733%	61.3518%	0.3466%	0.0000%
Jewish Raw	2	0	96	0	54	2	0
Jewish %	1.2987%	0.0000%	62.3377%	0.0000%	35.0649%	1.2987%	0.0000%

MAOA Gene Biochemistry

Pintar et al. (2-1-1981). Gene for monoamine oxidase type A assigned to the human X chromosome. Journal of Neuroscience 1(2): 166-175.

Kochersperger et al. (1986). Assignment of genes for human monoamine oxidase A and B to the X chromosome. Journal of Neuroscience Research 16(4): 601-616.

Bach et al. (7-1-1988). cDNA cloning of human liver monoamine oxidase A and B: molecular basis of differences in enzymatic properties. Proceedings of the National Academy of Sciences 85(13): 4934-4938.

Ozelius et al. (7-1988). Human monoamine oxidase (MAOA): chromosome position (Xp21-Xp11) and DNA polymorphism. Genomics 3(1): 53-58.

Black et al. (2-11-1991). Dinucleotide repeat polymorphism at the MAOA locus. Nucleic Acids Research 19(3): 689.

Grimsby et al. (5-1-1991). Human monoamine oxidase A and B genes exhibit identical exon-intron organization. Proceedings of the National Academy of Sciences 88(9): 3637-3641.

Chen et al. (8-25-1991). Structure of the human gene for monoamine oxidase type A. Nucleic Acids Research 19(16): 4537-4541.

Hinds et al. (7-1992). Characterization of a highly polymorphic region near the first exon of the human MAOA gene containing a GT dinucleotide and a novel VNTR motif. Genomics 13(3): 896-897.

Chen et al. (9-1992). Organization of the human monoamine oxidase genes and long-range physical mapping around them. Genomics 14(1): 75-82.

Zhu et al. (11-1-1992). Promoter organization and activity of human monoamine oxidase (MAO) A and B genes. Journal of Neuroscience 12(11): 4437-4446.

Shih et al. (1-1993). Structure and promoter organization of the human monoamine oxidase A and B genes. Journal of Psychiatry & Neuroscience 18(1): 25-32.

Shih et al. (1994). Identification of human monoamine oxidase (MAO) A and B gene promoters. Journal of Neural Transmission. Supplementum 41:27-33.

Denney et al. (9-1994). A new look at the promoter of the human monoamine oxidase A: gene mapping, transcription initiation sites, and capacity to drive luciferase expression. Journal of Neurochemistry 63(3): 843-856.

Denney et al. (1995). The promoter of the human monoamine oxidase A gene. Progress in Brain Research 106: 57-66.

Zhu et al. (10-1997). An extensive repeat structure down-regulates human monoamine oxidase A promoter activity independent of an initiator-like sequence. Journal of Neurochemistry 69(4): 1368-1373.

Sabol et al. (9-1998). A functional polymorphism in the monoamine oxidase A gene promoter. Human Genetics 103(3): 273-279.
- P1 promoter discovery
- Racial allele frequencies
- Large sample with no MAOA-2R

Benjamin et al. (2-2000). A novel expression based approach for assessing the inactivation status of human X-linked genes. European Journal of Human Genetics 8(2): 103-108.

Carrel and Willard. (3-17-2005). X-inactivation profile reveals extensive variability in X-linked gene expression in females. Nature 434(): 400-404.
- Supplements: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13

Nordquist and Oreland. (9-22-2006). Monoallelic expression of MAOA in skin fibroblasts. Biochemical and Biophysical Research Communications 348(2): 763-767.

Serotonin

Tuinier and Verhoeven. (6-1995). Dimensional classification and behavioral pharmacology of personality disorders; a review and hypothesis. European Neuropsychopharmacology 5(2): 135-146.

MAOA Metabolites

Nielsen et al. (1-1994). Suicidality and 5-hydroxyindoleacetic acid concentration associated with a tryptophan hydroxylase polymorphism. Archives of General Psychiatry 51(1): 34-38.

MAOA Enzyme

Bond et al. (10-15-1977). Properties of monoamine oxidase (MAO) in human blood platelets, plasma, lymphocytes and granulocytes. Clinica Chimica Acta 80(2): 317-326.

Cawthon et al. (8-1981). Differences in the structure of A and B forms of human monoamine oxidase. Journal of Neurochemistry 37(2): 363-372.

Weyler et al. (1990). Biochemistry and genetics of monoamine oxidase. Pharmacology & Therapeutics 47(3): 391-417.

Ramsay et al. (1994). Kinetic properties of cloned human liver monoamine oxidase A. Journal of Neural Transmission. Supplementum 41: 17-26.

Fogel and Maslinski. (1994). The FAD dependent amine oxidases in relation to developmental state of enterocyte. Journal of Neural Transmission. Supplementum 41: 95-99.

Fernandes and Soares-da-Silva. (1994). Role of monoamine oxidase and cathecol-O-methyltransferase in the metabolism of renal dopamine. Journal of Neural Transmission. Supplementum 41:101-105.

Naoi et al. (1994). Novel toxins and Parkinson’s disease: N-methylation and oxidation as metabolic bioactivation of neurotoxin. Journal of Neural Transmission. Supplementum 41: 197-205.

Banchelli et al. (1994). Histaminase activity of mesenteric artery of the rat. Journal of Neural Transmission. Supplementum 41: 445-448.

Son et al. (4-15-2008). Structure of human monoamine oxidase A at 2.2-A resolution: The control of opening the entry for substrates/inhibitors. PNAS 105(15): 5739-5744.
- Supplement

Alia-Klein et al. (5-7-2008). Brain monoamine oxidase A activity predicts trait aggression. The Journal of Neuroscience 28(19): 5099-5104.
- Subset of Fowler et al sample
- Aggression as MPQ personality outcome

Meulendyke et al. (9-15-2014). Elevated brain monoamine oxidase activity in SIV- and HIV-associated neurological disease. Journal of Infectious Disease 210(6): 904-912.
- Supplement

MAOA mRNA

Grimsby et al. (10-1990). Tissue distribution of human monoamine oxidase A and B mRNA. The Journal of Neurochemistry 55(4): 1166-1169.

Norrie Disease

Lan et al. (5-1989). Human monoamine oxidase A and B genes map to Xp 11.23 and are deleted in a patient with Norrie disease. Genomics 4(4): 552-559.

Levy et al. (8-1989). Localization of human monoamine oxidase-A gene to Xp11.23-11.4 by in situ hybridization: implications for Norrie disease. Genomics 5(2): 368-370.

MAOA/B Deletion Syndrome

Whibley et al. (10-2010). Deletion of MAOA and MAOB in a male patient causes severe developmental delay, intermittent hypotonia and stereotypical hand movements. European Journal of Human Genetics 18(10): 1095-1099.


Saito et al. (2-13-2013). MAOA/B deletion syndrome in male siblings with severe developmental delay and sudden loss of muscle tonus. Brain & Development: Epub ahead of print.

Brunner Syndrome

Brunner et al. (10-22-1993). Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A. Science 262(5133): 578-580.

Shih and Thompson. (9-1999). Monoamine oxidase in neuropsychiatry and behavior. American Journal of Human Genetics 65(3): 593-598.
- Review study
- Describes unpublished finding by Hwang and Shih that “urine analysis of 119 inmates from a prison in Taiwan showed no evidence for altered monoamine metabolism, suggesting MAO A deficiency.”

Nelson and Trainor. (7-2007). Neural mechanisms of aggression. Nature Reviews Neuroscience 8(7): 536-546.

Craig and Halton. (7-2009). Genetics of human aggressive behaviour. Human Genetics 126(1): 101-113.

Knockout Mice



MAOA-2R

Guo et al. (5-2008). The VNTR 2 repeat in MAOA and delinquent behavior in adolescence and young adulthood: Associations and MAOA promoter activity. European Journal of Human Genetics 16(5): 626-634.

Guo et al. (8-2008). The integration of genetic propensities into social-control models of delinquency and violence among male youths. American Sociological Review 73(4): 543-568.
- Supplement

Beaver et al. (1-2013). Exploring the association between the 2-repeat allele of the MAOA gene promoter polymorphism and psychopathic personality traits, arrests, incarceration, and lifetime antisocial behavior. Personality and Individual Differences 54(2): 164-168.

Roettger et al. (2013). MAOA genotype and longitudinal delinquency among males in the United States: the moderating role of parental incarceration and parental closeness.
- National Longitudinal Study of Adolescent Health, Waves I and IV
- Mother and father incarceration and closeness to child as environmental factors
- Self-reported criminal delinquency outcome
- Positive main effect (b=0.114, P < 0.036)
- MAOA-2R interacts with father closeness such that closeness significantly decreases criminal delinquency in men with MAOA-2R (b=-0.086, P < 0.013)

Beaver et al. (9-2014). The 2-repeat allele of the MAOA gene confers an increased risk for shooting and stabbing behaviors. Psychiatric Quarterly 85(3): 257-265.

MAOA-3R

Manuck et al. (7-24-2000). A regulatory polymorphism of the monoamine oxidase-A gene may be associated with variability in aggression, impulsivity, and central nervous system serotonergic responsivity. Psychiatry Research 95(1): 9-23.


Garpenstrand et al. (1-2003). A regulatory monoamine oxidase A promoter polymorphism and personality traits. Neuropsychobiology 46(4): 190-193.


Williams et al. (3-2003). Serotonin-related gene polymorphisms and central nervous system serotonin function. Neuropsychopharmacology 28(3): 533-541.
- Men with MAOA-3.5R or MAOA-4R averaged 17.70 ng/mL CSF 5-HIAA; men with MAOA-3R or MAOA-5R averaged 14.34 ng/mL
- “Similar effects were found in separate analyses for” white men and African-American men
- Negative finding for 5-HTTLPR epistasis (F=0.11, p=0.74)

Jacob et al. (9-2005). Cluster B personality disorders are associated with allelic variation of monoamine oxidase A activity. Neuropsychopharmacology 30(9): 1711-1718.


Rosenberg et al. (11-2006). The association of DNA sequence variation at the MAOA genetic locus with quantitative behavioural traits in normal males. Human Genetics 120(4): 447-459.
- Rare MAOA allele frequencies
- NEO personality outcome

Fowler et al. (8-15-2007). Evidence that brain MAO A activity does not correspond to MAO A genotype in healthy male subjects. Biological Psychiatry 62(4): 355-358.
- PET imaging
- Does not control for race

Yang et al. (11-2007). Association between monoamine oxidase A polymorphisms and anger-related personality traits in Korean women. Neuropsychobiology 56(1): 19-23.


De Neve and Fowler. (11-18-2009). The MAOA gene predicts credit card debt.
- National Longitudinal Study of Adolescent Health
- Positive main effect for credit card debt outcome

Fowler et al. (12-2009). Psychopathy trait scores in adolescents with childhood ADHD: the contribution of genotypes affecting MAOA, 5HTT and COMT activity. Psychiatric Genetics 19(6): 312-319.


Zhong et al. (12-31-2009). Monoamine Oxidase A gene (MAOA) associated with attitude towards longshot risks. PLOS One 4(12): e8516.
- Long-shot risk taking and insurance task outcomes
- MAOA-4R significantly associated with long-shot risk taking (p=0.006)

Gong et al. (9-2010). Association analysis between 12 genetic variants of ten genes and personality traits in a young Chinese Han population. Journal of Molecular Neuroscience 42(1): 120-126.
- Describes sample as being “324 females and 387 males,” but allele frequencies show 372 females and 293 males

Tikkanen et al. (2-28-2011). Psychopathy, PCL-R, and MAOA genotype as predictors of violent reconvictions. Psychiatry Research 185(3): 382-386.


Stetler et al. (7-16-2014). Association of low-activity MAOA allelic variants with violent crime in incarcerated offenders. Journal of Psychiatric Research 58: 69-75.
- Supplement

Ficks and Waldman. (9-2014). Candidate genes for aggression and antisocial behavior: A meta-analysis of association studies of the 5HTTLPR and MAOA-uVNTR. Behavior Genetics 44(5): 427-44.
- Supplement

MAOA-3R Gene-Environment Interaction

Caspi et al. (8-2-2002). Role of genotype in the cycle of violence in maltreated children. Science 297(5582): 851-854.
- Supplement
- Aged 26
- Abuse during ages 3-11 as environmental factor
- Conduct disorder, violent convictions, antisocial personality disorder, and Multidimensional Personality Questionnaire outcomes
- Composite outcome index for males: beta=-0.36, t=2.53, P=0.01
- MAOA-3R and MAOA-2R were 12% of the male group but 44% of violent convictions, 11% attributable risk fraction
- Kim-Cohen meta-analysis equivalent: beta=0.29, 95% confidence interval 0.10-0.49, 17.4% weight
- Byrd and Manuck meta-analysis equivalent for males: P=0.0050
- Byrd and Manuck meta-analysis equivalent for females: P=0.1285

Huang et al. (5-19-2004). An association between a functional polymorphism in the monoamine oxidase A gene promoter, impulsive traits and early abuse experiences. Neuropsychopharmacology 29(8): 1498-1505.
- MAOA-6R discovery - “Early abuse” as environmental factor
- Barratt Impulsivity Scale, Brown-Goodwin Aggression Scale, Buss-Durkee Hostility Inventory, major depressive disorder, bipolar disorder, and attempted suicide outcomes
- Positive for male impulsivity (F(1, 24)=4.60, p=0.042) and female suicide (chi-squared=6.543, df=1, p=0.011)

Foley et al. (7-2004). Childhood adversity, monoamine oxidase A genotype, and risk for conduct disorder. Archives of Psychiatry 61(7): 738-744.
- Aged 8-17
- Neglect, interparental violence, and inconsistent parental discipline as environmental factors
- Conduct disorder outcome
- Odds ratio 5.84, 95% confidence interval 0.44-77.97, p=0.09
- Negative finding incorrectly called “marginally significant”
- Kim-Cohen meta-analysis equivalent: beta=0.14, 95% confidence interval -0.05-0.34, 17% weight
- Byrd and Manuck meta-analysis equivalent: P=0.0200

Haberstick et al. (5-5-2005). Monoamine oxidase A (MAOA) and antisocial behaviorsin the presence of childhood and adolescent maltreatment. American Journal of Medical Genetics Part B 135B(1): 59-64.
- Supplement
- Average age 22
- National Longitudinal Study of Adolescent Health
- Childhood abuse and neglect and adolescent victimization as environmental factors
- Conduct disorder and violent convictions outcomes
- Negative finding, P=0.109
- Kim-Cohen meta-analysis equivalent: beta=0.14, 95% confidence interval -0.01-0.30, 28% weight
- Byrd and Manuck meta-analysis equivalent: P=0.1423

Nilsson et al. (1-15-2006). Role of monoamine oxidase A genotype and psychosocial factors in male adolescent criminal activity. Biological Psychiatry 59(2): 121-127.
- Aged 16 and 19
- Maltreatment or assault and multi-family household as environmental factors
- Stealing, vandalism, violence, and total crime outcomes by self-report
- Total criminality index: F=4.746, P=0.033, 1 degree of freedom
- Violence index: not significant
- Kim-Cohen meta-analysis equivalent: beta=0.51, 95% confidence interval 0.04-0.98, 3% weight
- Byrd and Manuck meta-analysis equivalent: P=0.0078

Meyer-Lindenberg et al. (4-18-2006). Neural mechanisms of genetic risk for impulsivity and violence in humans. PNAS 103(16): 6269-6274.
- Supplements: 1, 2, 3, 4, 5, 6
- Commentaries: 1, 2
- angry and fearful face matching, aversive picture memory task, and inhibitory control flanker task as environmental factors
- Positive fMRI activation outcomes for face matching (p<0.05), memory task (men only) (F(3,258)=3.0, p=0.03), and flanker task (men only)

Young et al. (6-2006). Interaction between MAO-A genotype and maltreatment in the risk for conduct disorder: failure to confirm in adolescent patients. American Journal of Psychiatry 163(6): 1019-1025.
- Subjects selected for conduct and substance use problems without controls
- Aged 12-18
- Colorado Adolescent Rearing Inventory of abuse or neglect as environmental factor
- Conduct disorder severity outcome
- Negative finding

Huizinga et al. (10-1-2006). Childhood maltreatment, subsequent antisocial behavior, and the role of monoamine oxidase A genotype. Biological Psychiatry 60(7): 677-683.
- Abuse and violent victimization before age 17 as environmental factors
- Conduct disorder, violent crime, violence disposition index, and antisocial personality disorder index, and antisocial behavior composite index outcomes
- Negative finding (beta= -0.525, standard error=0.370, t/z=-1.419, P=0.157)
- Byrd and Manuck meta-analysis equivalent: P=0.7794

Widom and Brzustowicz. (10-1-2006). MAOA and the “cycle of violence:” Childhood abuse and neglect, MAOA genotype, and risk for violent and antisocial behavior. Biological Psychiatry 60(7): 684-689.
- Not controlled for gender
- Cohort study used abuse cases (56-58% of cohort) and matched controls
- Source of claim that MAOA only affects white people. “Given the differences in the allele frequencies in the white and non-white populations for the MAOA VNTR promoter polymorphism (observed in this study), as well as other polymorphisms within the MAOA gene and throughout the genome, it could be that there are substantially different frequencies of other MAOA modulating polymorphisms in white and non-white populations. This could lead to the situation where genotype at the promoter VNTR polymorphism is more highly correlated with expression levels in one population than the other. Thus, our failure to extend the findings of the protective effect of high MAOA expression to the non-white sample in this study could simply be a reflection of the inadequacy of the promoter VNTR polymorphism as a proxy for overall MAOA expression in non-whites.” “Non-whites” are not broken down by race. Whites with MAOA-3R were 24% female. Non-whites with MAOA-3R were 43% female.
- Nikulina et al supposedly used the same sample. However, that study claimed non-Hispanic whites were 60.8% instead of 62.9% despite no change in the sample size listed. That study listed blacks as constituting 35.1% of the total and Hispanics as constituting the remaining 4.1%. Widom and Brzustowicz also listed Native Americans, Pacific Islanders, and “others.”
- A subgroup of this study were previously studied by Widom (1989). That study was 67% white and 31% black. - White MAOA-2R allele frequency: 1.05%
- Non-white MAOA-2R allele frequency: 4.17%
- MAOA-2R, MAOA-3.5R, MAOA-5R, and heterozygous females excluded from analysis
- Abuse before age 12 as environmental factor
- Crime, self-reported violence, conduct disorder, antisocial personality disorder, juvenile violent and antisocial behavior index, and lifetime violent and antisocial behavior index outcomes
- Abuse was not associated with non-white juvenile (beta=0.08, standard error=0.11, t=1.19, P “not significant”) or lifetime violent and antisocial behavior index (beta=0.13, standard error=0.12, t=1.86, P=0.06)
- Positive for white juvenile violent and antisocial behavior index (beta=-0.16, standard error=15, t=-2.54, p < 0.01)
- Negative finding for non-whites (juvenile: beta=0.06, standard error=0.28, t=0.67, P “not significant”; lifetime: beta=-0.01, standard error=0.29, t=-0.14, P “not significant”) and blacks (data not provided)
- Byrd and Manuck meta-analysis equivalent: P=0.0143

Kim-Cohen et al. (10-2006). MAOA, maltreatment, and gene-environment interaction predicting children’s mental health: new evidence and a meta-analysis. Molecular Psychiatry 11(10): 903-913.
- Also includes positive meta-analysis, using Caspi et al, Foley et al, Haberstick et al, Nilsson et al, and Kim-Cohen et al (beta=0.18, confidence interval 0.10-0.26, p < 0.001)
- Aged 7
- Abuse as environmental factor
- Antisocial behavior, emotional problems, and ADHD outcomes
- Significant opposite main effect for antisocial behavior (beta=0.19, t=2.34, p=0.019), ADHD (beta=0.18, t=2.23, p=0.026), and “composite mental health” (beta=0.19, t=2.40, p=0.017)
- Only positive for ADHD outcome (beta=-0.78, t=2.26, p=0.024) and “composite mental health” (beta=-0.84, t=2.09, p=0.037)
- Meta-analysis equivalent: beta=0.15, 95% confidence interval 0.01-0.28, 34.7% weight
- Byrd and Manuck meta-analysis equivalent: P=0.0145

Sjöberg et al. (3-5-2007). Adolescent girls and criminal activity: Role of MAOA-LPR genotype and psychosocial factors. American Journal of Medical Genetics Part B (Neuropsychiatric Genetics) 144B(2): 159-164.
- Female subjects only
- Aged 16 and 19
- Multi-family house and sexual abuse as environmental factors
- Violence index, stealing index, vandalism index, and total criminality index outcomes
- MAOA-4R or MAOA-5R interact with sexual abuse to increase vandalism index (F=4.315, df=1, P=0.040) and total criminality index (F=2.732, df=1, P=0.036)
- Byrd and Manuck meta-analysis equivalent: P=0.9082

Eisenberger et al. (5-1-2007). Understanding genetic risk for aggression: Clues from the brain’s response to social exclusion. Biological Psychiatry 61(9): 1100-1108.
- Does not control for race
- Cyberball social exclusion task as environmental factor
- Spielberger Trait Anger scale and Brief Symptom Inventory for aggression and interpersonal hypersensitivity and fMRI dorsal anterior cingulated cortex activation outcomes
- Positive main effects for aggression (F(2,29)=3.68, p<0.05) and for interpersonal hypersensitivity (excluding heterozygotes) (t(19)=2.32, p<0.05)
- Positive interaction for dorsal anterior cingulated cortex activation outcome at 6,36,32 (F(2,28)=4.07, p<0.05)

Frazzetto et al. (5-2007). Early trauma and increased risk for physical aggression during adulthood: the moderating role of MAOA genotype. PLOS One 2(5): e486.
- Men and women assessed
- Included psychiatric admits
- Bandelow et al childhood traumatic life events questionnaire as environmental factor
- Aggression questionnaire outcome
- F = 7.04, p=0.009, 6.6% of variance explained

Oreland et al. (6-2007). Monoamine oxidases – activities, genotypes and the shaping of behaviour. Journal of Neural Transmission 114(6): 817-822.

Reif et al. (11-2007). Nature and nurture predispose to violent behavior: serotonergic genes and adverse childhood environment. Neuropsychopharmacology 32(11): 2375-2383.
- Childhood adverse environmental index as environmental factor
- Compared violent criminals to criminals without violent offenses
- Positive main effect (odds ratio = 2.3, 95% confidence interval 1.1-4.7, p=0.027)
- Positive epistasis with 5-HTTLPR with adverse environment (p<0.0001)

Vanyukov et al. (12-2007). The MAOA promoter polymorphism, disruptive behavior disorders, and early onset substance use disorder: Gene-environment interaction. Psychiatric Genetics 17(6): 323-332.
- Aged 10 to 19
- Child Assessment of Parental Involvement and Behavior scale as environmental factor
- Attention deficit hyperactivity disorder, conduct disorder, oppositional defiant disorder, and substance use disorder outcomes
- MAOA-4R interacts with father’s parental scale to decrease conduct disorder (odds ratio=0.380, 95% confidence interval: 0.179-0.805, P=0.011 for MAOA-4R alone) and increase ADHD (odds ratio=3.299, 95% confidence interval: 1.479-7.356, P=0.004 for MAOA-3R versus MAOA-4R and odds ratio=1.974, 95% confidence interval: 1.230-3.168, P=0.005 for MAOA-4R alone) - Byrd and Manuck meta-analysis equivalent: P=0.6517

Ducci et al. (3-2008). Interaction between a functional MAOA locus and childhood sexual abuse predicts alcoholism and antisocial personality disorder in adult women. Molecular Psychiatry 13(3): 334-347.
- Supplements: 1, 2
- All subjects have at least 25% Southwestern Native-American ancestry
- Also examined MAOA SNPs
- All 210 males excluded due to 90% having alcoholism and only 17% (of 126 asked) having experienced sexual abuse
- One subject with a rare allele was unaccounted for
- Sexual abuse before age 16 as environmental factor
- Antisocial personality disorder, antisocial personality disorder symptom count, and alcohol use disorder outcomes
- Positive main effect for antisocial personality disorder with alcohol use disorder (degrees of freedom=1, chi-squared=5.2, P=0.02), but not if sexually abused females were excluded
- MAOA-3R interacts with sexual abuse to increase antisocial personality disorder with alcohol use disorder (degrees of freedom=1, chi-squared=7.17, P=0.007)
- MAOA-3R interacts with sexual abuse to increase antisocial personality disorder symptom count (ANOVA: degrees of freedom=2, F=8.0, P=0.0006, regression model explained 22% of variance)
- Identified 5 MAOA haplotypes with haplotype B (the most common MAOA-3R-associated haplotype) interacting with sexual abuse to increase alcohol use disorder (degrees of freedom=1, chi-squared=10.57, P=0.002) and antisocial personality disorder with alcohol use disorder (degrees of freedom=1, chi-squared=16.12, P=0.00001)
- Byrd and Manuck meta-analysis equivalent: P=0.0002

Prichard et al. (3-5-2008). No evidence for interaction between MAOA and childhood adversity for antisocial behavior. American Journal of Medical Genetics B (Neuropsychiatric Genetics) 147B(2): 228-232.
- Adversity exposures as environmental factor using the following criteria: lack of affection, anxiety or emotional trouble, parental drug or alcohol use, family conflict, parental divorce or separation, neglect, authoritarian parenting, psychological abuse, witnessing physical or sexual abuse, physical abuse, sexual abuse, poverty
- Principle component factor as outcome using the following criteria: sex before age 15, leaving home before age 18, living with a partner before age 18, childbirth before age 18, smoking, past hazardous drinking, marijuana use before age 16, weekly or more marijuana use, frequent financial problems, less than 5 of secondary school education, unemployment, police problems or court appearance within last 6 months

Passamonti et al. (4-15-2008). Genetically dependent modulation of serotonergic inactivation in the human prefrontal cortex. NeuroImage 40(3): 1264-1273.
- Inhibitory control task as environmental factor
- Anterior cingulate cortex and orbitofrontal cortex BOLD fMRI imaging outcomes
- Non-significant MAOA effect for fMRI imaging of anterior cingulate cortex and orbitofrontal cortex
- Positive anterior cingulated cortex imaging outcome for MAOA x 5-HTTLPR epistasis

McDermott et al. (2-17-2009). Monoamine oxidase A gene (MAOA) predicts behavioral aggression following provocation. PNAS 106(7): 2118-2123.
- Supplement - College students, age unknown
- Does not control for race
- Amount of money taken from subject in game as environmental factor
- Simulated hot sauce administration to opponents game outcome
- Positive main effect (numbers not given)
- Positive gene-environment interaction (Z=1.85, P=0.032)

Weder et al. (3-1-2009). MAOA genotype, maltreatment, and aggressive behavior: the changing impact impact of genotype at varying levels of trauma. Biological Psychiatry 65(5): 417-424.
- Aged 5-15
- Does not control for gender
- Positive for total group and for African Americans and biracial as a separate group
- Total trauma exposure score (0 to 2) as environmental factor - Aggression as Achenbach Teacher’s Report outcome

Van der Vegt et al. (8-2009). High activity of monoamine oxidase A is associated with externalizing behaviour in maltreated and nonmaltreated adoptees. Psychiatric Genetics 19(4): 209-211.
- Does not control for race, but does for country of origin
- Race not identified

Hart and Marmorstein. (8-2009). Neighborhoods and genes and everything in between: Understanding adolescent aggression in social and biological contexts. Development and Psychopathology 21(3): 961-973.
-

Aslund et al. (3-2011). Maltreatment, MAOA, and delinquency: Sex differences in gene-environment interaction in a large population-based cohort of adolescents. Behavior Genetics 41(2): 262-272.
- Aged 17-18
- Survey of Adolescent Life in Vestmanland (SALVe-2006)
- Non-Scandinavian subjects not identified by race
- MAOA-5R lumped with MAOA-3.5R and MAOA-4R as MAOA-L
- Maltreatment summation index as environmental factor
- Vandalism, stealing, violence, and total delinquency indices outcomes
- Positive main effect of MAOA-3R (when not controlled for Scandinavian ethnicity) for total delinquency (degrees of freedom=2, F=3.78, P=0.023), stealing (degrees of freedom=2, F=5.40, P=0.005), and violence (degrees of freedom=2, F=4.68, P=0.009)
- Positive gene-environment interaction for total delinquency (degrees of freedom=2, F=14.56, P<0.001), vandalism (degrees of freedom=2, F=4.97, P=0.007), stealing (degrees of freedom=2, F=19.66, P<0.001), and violence (degrees of freedom=2, F=21.27, P<0.001)
- Positive gene-environment interaction in boys for total delinquency (degrees of freedom=3, chi-squared=57.21, P<0.001), vandalism (degrees of freedom=3, chi-squared =47.85, P<0.001), stealing (degrees of freedom=3, chi-squared =53.77, P<0.001), and violence (degrees of freedom=3, chi-squared=59.56, P<0.001)
- Positive gene-environment interaction in girls for total delinquency (degrees of freedom=5, chi-squared =115.71, P<0.001), vandalism (degrees of freedom=5, chi-squared =108.01, P<0.001), stealing (degrees of freedom=5, chi-squared =51.98, P<0.001), and violence (degrees of freedom=5, chi-squared=57.40, P<0.001)

Takahashi et al. (2-2011). Brain serotonin receptors and transporters: Initiation vs. termination of escalated aggression. Psychopharmacology 213(2-3): 183-212.

Kieling et al. (3-2013). Gene-environment interaction in externalizing problems among adolescents: evidence from the Pelotas 1993 Birth Cohort Study. The Journal of Child Psychology and Psychiatry: 54(3): 298-304.
- Aged 15
- Skin color controlled
- Pelotas 1993 Birth Cohort Study
- Childhood maltreatment before age 15 as environmental factor
- Negative finding for Strengths and Difficulties Questionnaire greater than 95% score for conduct disorder at age 15, P=0.823
- Conduct disorder scores declined from age 11 (2.5) to age 15 (2.3)

Kuepper et al. (3-13-2013). MAOA-uVNTR genotype predicts interindividual differences in experimental aggressiveness as a function of the degree of provocation. Behavioural Brain Research: epub ahead of print.
- Supplement
- Noise aversive stimuli as environmental factor for reactive aggression
- Competitive reaction time task (reactive aggression) and Freiburg Personality Inventory self-report general aggression scale outcomes
- Positive for high (F(2,234)=3.883, P < 0.05) and extreme (F(2,235)=8.166, P < 0.001) provocation effects on reactive aggression
- Not positive for gene interaction with gender

Ernst et al. (3-16-2013). Genetic variation in MAOA modulates prefrontal cortical regulation of approach-avoidance reactions. Neuropsychobiology 67(3): 168-180.


Haberstick et al. (5-28-2013). MAOA genotype, childhood maltreatment, and their interaction in the etiology of adult antisocial behaviors. Biological Psychiatry: epub ahead of print.
- Supplement - National Longitudinal Study of Adolescent Health Wave IV (excluded previous sample from Haberstick et al 2005)
- White MAOA-2R allele frequency: 0.298%
- Black MAOA-2R allele frequency: 4.79%
- Abuse before age 18 as environmental factor
- Childhood antisocial behavior, adult antisocial behavior, violent crime, Mini-International Personality Item Pool anger hostility scale, and composite antisocial index outcomes
- In black males , abuse was not associated with composite antisocial index (beta=0.15, standard error=0.16, t=0.96, 95% confidence interval -0.16 to 0.47), childhood antisocial behavior (beta=0.44, standard error=0.31, t=1.43, P=0.15), adult antisocial behavior (beta=0.20, standard error=0.17, t=1.19, P=0.24), violent crime (beta=0.01, standard error=0.05, t=0.23, P=0.82), or anger hostility scale (beta=0.12, standard error=0.43, t=0.28, P=0.78)
- Negative finding for composite antisocial index for white males (beta=-0.13, standard error=0.08, t=-1.67, 95% confidence interval -0.29 to 0.02, P=0.10) and black males (beta=-0.15, standard error=0.20, t=-0.76, 95% confidence interval -0.55 to 0.25, P=0.45)
- Positive main effect for anger hostility scale in white males (95% confidence interval 0.15-0.87, P=0.006)
- Positive main effect for violent crime in black males (95% confidence interval -0.11 to -0.02, P=0.006)

Byrd and Manuck. (6-17-2013). MAOA, childhood maltreatment, and antisocial behavior: meta-analysis of a gene-environment interaction. Biological Psychiatry: epub ahead of print.
- Used Caspi et al, Foley et al, Haberstick et al, Huizinga et al, Kim-Cohen et al, Nilsson et al, Widom and Brzustowicz, Frazzetto et al, Sjoberg et al, Vanyukov et al, Ducci et al, Hart and Marmorstein, Prom-Wormley et al, van der Vegt et al, Weder et al, Beach et al, Beaver et al, Derringer et al, Edwards et al, Enoch et al, Waleschlag et al, Aslund et al, Lee, Reti et al, Cicchetti et al, Fergusson et al, and McGrath et al
- Total sample size: > 18,400 for all 27 studies, 11,064 subjects in studies with men, 7588 subjects in studies with women
- Having MAOA-2R, MAOA-3R, or MAOA-5R with maltreatment as an environmental factor is significantly associated with male antisocial behavior (P=2 x 10^-7, publication bias would require > 105 missing studies with 447 samples to explain away), male violent behavior (P=0.01), and male nonviolent antisocial behavior (P=4 x 10^-4)
- Negative findings for MAOA=2R, MAOA-3R, or MAOA-5R with maltreatment as an environmental factor significantly affecting female antisocial behavior (P=0.77)
- Having MAOA-3.5R or MAOA-4R with childhood maltreatment as an environmental factor is significantly associated with female antisocial behavior (P=0.020)

Tiihonen et al. (10-28-2014). Genetic background of extreme violent behavior. Molecular Psychiatry: epub ahead of print.
- Supplement
- Allele frequencies of rare MAOA alleles are not given, but no copies of MAOA-2R are present
- Violent crime, extremely violent crime (each committing 10 or more crimes of murder, manslaughter, attempted homicide, or battery), and homicide (in replication cohort) outcomes
- Negative finding for HTR2B
- GWAS identified CDH13 SNP rs11649622
- Positive main effect for violent crime (P=2.93 x 10^-5, odds ratio=1.708, 9% attributable risk fraction, 95% confidence interval: 4-15%) and extremely violent crime (P=1.6 x 10^-4, odds ratio=2.662, 16% attributable risk fraction, 95% confidence interval: 8-24%)
- Positive main effect in men for violent crime (P=4 x 10^-4, odds ratio=1.661, 95% confidence interval: 1.252-2.204) and extremely violent crime (P=4 x 10^-4, odds ratio=2.617, 95% confidence interval: 1.540-4.445)
- Positive main effect in women for violent crime (P=0.0226, odds ratio=1.898, 95% confidence interval: 1.094-3.291) but not for extremely violent crime (P=0.2118, odds ratio=3.143, 95% confidence interval: 0.521-18.97)
- Negative with childhood maltreatment as an environmental factor (odds ratio=1.62)

MAOA-3R Gene-Hormone Interaction

Zhu et al. (12-1994). Bidirectional promoter of human monoamine oxidase A (MAO A) controlled by transcription factor Sp1. Journal of Neuroscience 14(12): 7393-7403.

Shih et al. (1995). Expression of human monoamine oxidase (MAO) A gene controlled by transcription factor Sp1. Progress in Brain Research 106: 49-56.

Sjöberg et al. (1-2008). A non-additive interaction of a functional MAO-A VNTR and testosterone predicts antisocial behavior. Neuropsychopharmacology 33(): 425-430.
- Brown-Goodwin aggression scores and antisocial personality disorder outcomes

Romanuik et al. (9-24-2010). LNCaP Atlas: Gene expression associated with in vivo progression to castration-recurrent prostate cancer. BMC Medical Genomics 3(43): 1-19.

MAOA Epigenetics

Wong et al. (8-16-2010). A longitudinal study of epigenetic variation in twins. Epigenetics 5(6): 516-526.
- Male methylation lower, less variable, and more heritable than female methylation

Philibert et al. (7-2011). Gene environment interactions with a novel variable monoamine oxidase A transcriptional enhancer are associated with antisocial personality disorder. Biological Psychology 87: 366-371.
- Supplement
- P2 promoter discovery
- P2 9R allele had less methylation than 10R in women only (p < 0.03)
- Abuse as environmental factor
- Antisocial personality disorder outcome
- Only positive results were in women for environment interaction with P2 (beta=-0.229, p=0.007) and environmental interaction with P1 and P2 (r(96)=0.458, p < 0.001)

MAOA-3R Epistasis

Strous et al. (7-1-2003). Aggressive behavior in schizophrenia is associated with the low enzyme activity COMT polymorphism: A replication study. American Journal of Medical Genetics B (Neuropsychiatric Genetics) 120B(1): 29-34.
- Sample was 63% Sephardic Jew and 37% Ashkenazi Jew with allele frequencies: 1.3% MAOA-2R, 62.3% MAOA-3R, 35.1% MAOA-4R, 1.3% MAOA-5R
- Subjects selected for schizophrenia without controls
- Life History of Aggression Scale outcome
- MAOA-3R or MAOA-5R x COMT Met/Met x female gender positive interaction (F(2,105)=3.6, p=0.031)

Qian et al. (6-18-2009). Association study of intelligence of attention deficit hyperactivity disorder children in China. Beijing Da Xue Xue Bao 41(3): 285-290.

Qian et al. (5-2010). Gene-gene interaction between COMT and MAOA potentially predicts the intelligence of attention-deficit hyperactivity disorder boys in China. Behavior Genetics 40(3): 357-365.
- COMT Val/Val x MAOA-3R average IQ=106.7, 95% confidence interval 103.7-109.8; COMT Val/Val x MAOA-4R average IQ=98.0, 95% confidence interval 93.5-102.6

Kang et al. (7-2010). Association study between antipsychotic-induced restless legs syndrome and polymorphisms of monoamine oxidase genes in schizophrenia. Human Psychopharmacology 25(5): 397-403.
- Subjects selected for schizophrenia without controls
- International Restless Legs Syndrome Study Group rating scale outcome
- MAOA-3R x MAOB A644G SNP x gender interaction (F=4.05 & p=0.047 for men, F=5.00 & p=0.028 for women but in opposite direction)

MAOA Single-Nucleotide Polymorphisms

Balciuniene et al. (2-2001). The geographic distribution of monoamine oxidase haplotypes supports a bottleneck during the dispersion of modern humans from Africa. Journal of Molecular Evolution 52(2): 157-163.
- Haplotype frequency differences between Africans and non-Africans suggest a demographic bottleneck or positive selection.

Gilad et al. (1-22-2002). Evidence for positive selection and population structure at the human MAO-A gene. PNAS 99(2): 862-867.

Eccles et al. (5-2012). A unique demographic history exists for the MAO-A gene in Polynesians. Journal of Human Genetics 57(5): 294-300.
- Supplements: 1, 2, 3, 4
- Supplementary figure 1 (supplement 1) has mislabeled bar graphs

Tielbeek et al. (10-15-2012). Unraveling the genetic etiology of adult antisocial behavior: A genome-wide association study. PLOS One 7(10): e45086.
- Supplements: 1, 2, 3, 4, 5
- Genome-wide association study
- Aged 18-81
- Does not control for gender
- Antisocial personality disorder outcome
- No SNPs had genome-wide significance, including 7 MAOA SNPs.
- All 278,570 SNPs collectively explained 55% of variance

Redin et al. (11-2014). Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing. Journal of Medical Genetics 51(11): 724-736.
- Supplements: 1, 2


MAOA CA Repeat Polymorphisms

Vanyukov et al. (11-29-1995). A dinucleotide repeat polymorphism at the gene for monoamine oxidase A and measures of aggressiveness. Psychiatry Research 59(1-2): 35-41.
- Negative finding

MAOA Animal Models

Gibbons. (5-7-2004). Tracking the evolutionary history of a “warrior” gene. Science 304(5672): 818.
- Origin of “warrior gene” label

MAOA Research Criticism, Law, & “Ethics”

Baker et al. (Winter & Spring 2006). Behavioral genetics: The science of antisocial behavior. Law and Contemporary Problems 69(1-2): 7-46.

Kaplan. (Winter & Spring 2006). Misinformation, misrepresentation, and misuse of human behavioral genetics research. Law and Contemporary Problems 69(1-2): 47-80.

Garland and Frankel. (Winter & Spring 2006). Considering convergence: A policy dialogue about behavioral genetics, neuroscience, and law. Law and Contemporary Problems 69(1-2): 101-113.

Denno. (Winter & Spring 2006). Revisiting the legal link between genetics and crime. Law and Contemporary Problems 69(1-2): 209-257.

Kaye. (Winter & Spring 2006). Behavioral genetics research and criminal DNA databases. Law and Contemporary Problems 69(1-2): 259-299.

Beecher-Monas and Garcia-Rill. (Winter & Spring 2006). Genetic predictions of future dangerousness: Is there a blueprint for violence? Law and Contemporary Problems 69(1-2): 301-341.

Bernet et al. (11-2007). Bad nature, bad nurture, and testimony regarding MAOA and SLC6A4 genotyping at murder trials. Journal of Forensic Sciences 52(6): 1362-1371.

Hunter. (9-2010). The Psycho Gene. EMBO Reports 11(9): 667-669.
- Falsely claimed “Brunner’s syndrome … having only been identified in five males…”
- Falsely claimed “MAOA-L variant … occurs in about 40% of the population.”

Gillett & Tamatea. (2012). The warrior gene: Epigenetic considerations. New Genetics and Society 31(1): 41-53.

Related Research on Antisocial Personality Disorder & Aggression



MAOA, Depression, Bipolar Disorder, & Suicide

Craddock et al. (8-14-1995). No evidence for allelic association between bipolar disorder and monoamine oxidase A gene polymorphisms. American Journal of Medical Genetics 60(4): 322-324.

Lim et al. (8-14-1995). Evidence for a genetic association between alleles of monoamine oxidase A gene and bipolar affective disorder. American Journal of Medical Genetics 60(4): 325-331.

Muramatsu et al. (9-19-1997). Monoamine oxidase genes polymorphisms and mood disorder. American Journal of Medical Genetics 74(5):494-496.
- Depression and bipolar outcomes
- Negative findings for MAOA-CA, MAOA-VNTR (not P1 or P2), MAOA-RFLP, and MAOB-GT

Kunugi et al. (7-1999). A functional polymorphism in the promoter region of monoamine oxidase-A gene and mood disorders. Molecular Psychiatry 4(4): 393-395.
- MAOA-2R discovery
- Asian MAOA-2R allele frequency: 1.0%
- Depression, bipolar disorder, and suicide outcomes
- Negative finding (p=0.46)
- Fan et al depression meta-analysis equivalent: in men, odds ratio=1.26, 95% confidence interval 0.60-2.66; and in women, odds ratio=0.96, 95% confidence interval 0.62-1.49
- Fan et al bipolar disorder meta-analysis equivalent: in men, odds ratio=1.14, 95% confidence interval 0.60-2.14; and in women, odds ratio=1.08, 95% confidence interval 0.75-1.58

Furlong et al. (8-20-1999). Analysis of the monoamine oxidase A (MAOA) gene in bipolar affective disorder by association studies, meta-analyses, and sequencing of the promoter. American Journal of Medical Genetics (Neuropsychiatric Genetics) 88(4): 398-406.
- Bipolar disorder and depression outcomes
- Also includes a bipolar meta-analysis, using Craddock et al, Kawada et al, Nothen et al, Lim et al, Muramatsu et al, and Parsian and Todd
- Negative findings for MAOA-CA (for depression: chi-squared=3.349, 3 df, p=0.34; for bipolar disorder: chi-squared=0.317, 3df, p=0.96), MAOA-Fnu (for depression: chi-squared=0.821, 1 df, p=0.37; for bipolar disorder: chi-squared=0.004, 1 df, p=0.95), and MAOA-3R (for depression: chi-squared=0.958, 2 df, p=0.62; for bipolar disorder: chi-squared=0.082, 2 df, p=0.96)
- Positive meta-analysis for MAOA-CA in whites (odds ratio 1.55, 95% confidence interval 1.06-2.28, p < 0.02) and Japanese (odds ratio 2.65, 95% confidence interval 1.29-5.45)
- Positive meta-analysis for MAOA-Fnu only in white women (odds ratio 0.70, confidence interval 0.49-0.99)
- Fan et al depression meta-analysis equivalent: in men, odds ratio=0.72, 95% confidence interval 0.34-1.52; and in women, odds ratio=1.31, 95% confidence interval 0.85-2.02
- Fan et al bipolar disorder meta-analysis equivalent: in men, odds ratio=0.72, 95% confidence interval 0.35-1.50; and in women, odds ratio=1.05, 95% confidence interval 0.65-1.69

Ho et al. (2-7-2000). Genetic associations with clinical characteristics in bipolar affective disorder and recurrent unipolar depressive disorder. American Journal of Medical Genetics (Neuropsychiatric Genetics) 96(1): 36-42.
- Subjects selected for depression and bipolar disorder without controls
- Suicide outcome
- Positive for women (p=0.035)

Schulze et al. (12-2000). Association between a functional polymorphism in the monoamine oxidase A gene promoter and major depressive disorder. American Journal of Medical Genetics (Neuropsychiatric Genetics) 96(6): 801-803.
- Main effect of MAOA-3.5R, MAOA-4R, or MAOA-5R in women (p=0.029)
- Fan et al depression meta-analysis equivalent: in men, odds ratio=1.28, 95% confidence interval 0.45-3.61; and in women, odds ratio=1.37, 95% confidence interval 0.87-2.14

Ono et al. (4-8-2002). No evidence of an association between a functional monoamine oxidase A gene polymorphism and completed suicides. American Journal of Medical Genetics (Neuropsychiatric Genetics) 114(3): 340-342.
- Asian MAOA-2R allele frequency: 0.47%
- Negative finding (p=0.34)

Gutierrez et al. (12-2004). Association analysis between a functional polymorphism in the monoamine oxidase A gene promoter and severe mood disorders. Psychiatric Genetics 14(4): 203-208.
- Depression, bipolar disorder, suicide, psychosis, seasonal symptoms, Hamilton index, comorbidity, recurrence, episode number, episode length, psychiatric admissions, and family history of mental disorder outcomes
- Positive MAOA-3.5R/4R/5R link in bipolar women to longer psychiatric admission (F=4.604, p=0.037)
- Fan et al depression meta-analysis equivalent: in men, odds ratio=0.97, 95% confidence interval 0.51-1.84; and in women, odds ratio=1.01, 95% confidence interval 0.67-1.52
- Fan et al bipolar disorder meta-analysis equivalent: in men, odds ratio=1.35, 95% confidence interval 0.57-3.21; and in women, odds ratio=1.02, 95% confidence interval 0.59-1.76

Yu et al. (9-2005). Association study of a monoamine oxidase A gene promoter polymorphism with major depressive disorder and antidepressant response. Neuropsychopharmacology 30(9): 1719-1723.
- Sample sizes of control subjects by gender listed incorrectly
- Asian MAOA-2R allele frequency: 0.92%
- Major depressive disorder and Hamilton Depression Rating Scale outcomes
- Main effect of MAOA-4R for depression women (chi-squared=6.93, df=1, p=0.009), for men (chi-squared=6.27, df=1, p=0.015), and for both (chi-squared=12.48, p < 0.001)
- Main effect of MAOA-3R to improve the effect of 4-weeks of fluoxetine on Hamilton Depression Rating Scale in women (p=0.024)
- Fan et al depression meta-analysis equivalent: in men, odds ratio=2.07, 95% confidence interval 1.17-3.67; and in women, odds ratio=1.64, 95% confidence interval 1.13-2.37

Lin et al. (5-24-2008). Association analysis of monoamine oxidase A gene and bipolar affective disorder in Han Chinese. Behavioral and Brain Functions 4(21): 1-6.
- Unknown allele frequencies of MAOA-4R and MAOA-5R lumped together as the “long allele”
- MAOA-3R with MAOA-CA significantly not associated with bipolar disorder in women (odds ratio=1.22, 95% confidence interval: 0.41-3.67, p=0.72). For men, association is listed as significant with p=0.01 but 95% confidence interval of odds ratio includes null value (odds ratio=12.64, 95% confidence interval: 0.69-232.88)
- Fan et al bipolar meta-analysis equivalent: in men, odds ratio=0.61, 95% confidence interval 0.28-1.32; and in women, odds ratio=1.29, 95% confidence interval 0.71-2.33

Huang et al. (9-2008). Neither single-marker nor haplotype analyses support an association between monoamine oxidase A gene and bipolar disorder. European Archives of Psychiatry and Clinical Neuroscience 258(6): 350-356.
- Asian MAOA-2R allele frequency: 0.73%
- Negative finding (p=0.525)

Huang et al. (2009). Association of monoamine oxidase A (MAOA) polymorphisms and clinical subgroups of major depressive disorders in the Han Chinese population. World Journal of Biological Psychiatry 10(4 Part 2): 544-551.
- Outcomes were major depressive disorder, Hamilton depression rating scale (severe is > 24), and family history of first-degree relatives with depression or bipolar disorder
- Asian MAOA-2R allele frequency: 0.95%
- Only positive in women for linking MAOA-3R to severe depression (p=0.041) and for linking MAOA-EcoRV to depression (p=0.049), to depression with family history (p=0.047), and to severe depression (p=0.017)
- Fan et al depression meta-analysis equivalent: in men, odds ratio=1.23, 95% confidence interval 0.76-1.99; and in women, odds ratio=0.91, 95% confidence interval 0.64-1.28

Fan et al. (2-2010). Meta-analysis of the association between the monoamine oxidase-A gene and mood disorders. Psychiatric Genetics 20(1): 1-7.
- Used Craddock et al, Lim et al, Muramatsu et al, Parsian and Todd, Sasaki et al, Furlong et al, Kunugi et al, Schulze et al, Preisig et al, Lin et al (2000), Syagailo et al, Tadic et al, Gutierrez et al, Yu et al, Huang et al (2007), Lin et al (2008), and Huang et al (2008)
- Only positive for major depressive disorder in Asians (odds ratio=1.23, 95% confidence interval 1.02-1.47, p=0.03) and Asian men (odds ratio=1.47, 95% confidence interval 1.06-2.05, p=0.02) with MAOA-3.5R, MAOA-4R, or MAOA-5R
- Only positive for bipolar disorder in whites with MAOA T941G SNP (odds ratio=1.28, 95% confidence interval 1.01-1.62, p=0.04) and MAOA-CA a6 (odds ratio=1.35, 95% confidence interval 1.11-1.64, p=0.002) alleles and in white women with MAOA T941G (odds ratio=1.36, 95% confidence interval 1.03-1.81) and MAOA-CA a5 (odds ratio=1.44, 95% confidence interval 1.04-1.99, p=0.03) and a6 (odds ratio=1.41, 95% confidence interval 1.12-1.78, p=0.004) alleles

Hung et al. (2-2012). Monoamine oxidase A gene polymorphism and suicide: An association study and meta-analysis. Journal of Affective Disorders 136(3): 643-649.
- Also includes negative suicide meta-analysis, using Ho et al, Ono et al, Huang et al, Courtet et al, Steiger et al, Lung et al, and Hung et al, for males (odds ratio=0.85, 95% confidence interval 0.67-1.10, p=0.22) and females (odds ratio=1.13, 95% confidence interval 0.94-1.36, p=0.21)
- Asian MAOA-2R allele frequency: 0.50%
- Negative finding (p=0.34)

Nikulina et al. (2-15-2012). Child abuse and neglect, MAOA, and mental health outcomes: a prospective examination. Biological Psychiatry 71(4): 350-357
- Supplement
- Same sample as Widom and Brzustowicz with additional racial data
- Does not control for gender
- Physical abuse, sexual abuse, and neglect before age 12 as environmental factors
- Depression, dysthymia, and alcohol abuse outcomes
- MAOA-4R interacted with physical abuse or with having experienced multiple forms of abuse (physical abuse, sexual abuse, or neglect) to affect dysthymia symptoms in women only
- MAOA-3R and MAOA-4R interacted with race and sexual abuse to affect depression, dysthymia, and alcohol abuse (beta=-0.19, P < 0.05 for depression, beta=-0.22, P < 0.05 for dysthymia, beta=-0.27, P < 0.01 for alcohol abuse). MAOA-3R decreased symptoms in sexually abused whites. MAOA-4R decreased symptoms in sexually abused non-whites. (Gender is not controlled, and racial groups differ in gender proportions with each allele. See Widom and Bruzstowicz, 2006)

Chen et al. (1-10-2013). The MAOA gene predicts happiness in women. Progressive in Neuro-Psychopharmacology & Biological Psychiatry 40: 122-125.

Melas et al. (3-2013). Genetic and epigenetic associations of MAOA and NR3C1 with depression and childhood adversities. International Journal of Neuropsychopharmacology: epub ahead of print.
- Supplements: 1, 2, 3, 4, 5, 6
- Subjects were Swedish citizens but race is unidentified and not controlled. Of the 11% who are non-Swedish, most have “Nordic origin that is primarily Finnish.” (Source cited does not give this information.)
- Large sample with no MAOA-2R
- Prior to age 18, early parental death, parental divorce, financial problems, and other familial constraints as environmental factors
- Major Depression Inventory, mixed anxiety depression, dysthymia, and MAOA and NR3C1 methylation outcomes
- Main effect of MAOA-3R on depression in women (odds ratio=1.7, 95% confidence interval 1.2-2.4)
- Positive MAOA-3R x environment interaction for depression in women (Wald=16.4, df=5, p=0.006), in men (Wald=13.4, df=5, p=0.02), and both (Wald=26.8, df=5, p < 0.001)
- Positive association of epigenetic hypomethylation of MAOA with depression in women (p=0.001)
- Positive interaction of MAOA-3R x early parental death effect on NR3C1 hypermethylation (F=23.484, p < 0.001)

Ma et al. (7-2013). Association between MAOA-u VNTR polymorphism and its interaction with stressful life events and major depressive disorder in adolescents. Zhongguo Dang Dai Er Ke Za Zhi 15(7): 563-568.

MAO Inhibitors

Robinson et al. (10-5-1983). Plasma levels of catecholamines and dihydroxyphenylglycol during antidepressant drug treatment. Journal of Clinical Psychopharmacology 3(5): 282-287.

Whitaker-Azmitia et al. (10-1994). Effects of gestational exposure to monoamine oxidase inhibitors in rats: preliminary behavioral and neurochemical studies. Neuropsychopharmacology 11(2): 125-132.

Witkin et al. (4-4-2013). Further evaluation of the neuropharmacological determinants of the antidepressant-like effects of curcumin. CNS Neurological Disorders – Drug Targets: epub ahead of print.

MAOA & Panic Disorder



MAOA & Schizophrenia

Coron et al. (6-1-1996). Association study between schizophrenia and monoamine oxidase A and B DNA polymorphisms. Psychiatry Research 62(3): 221-226.
- Negative finding for MAOA EcoRV polymorphism

Syagailo et al. (3-8-2001). Association analysis of the functional monoamine oxidase A gene promoter polymorphism in psychiatric disorders. American Journal of Medical Genetics (Neuropsychiatric Genetics) 105(2): 168-171.
- Negative finding for depression (p=0.731), bipolar disorder (p=0.863), and schizophrenia (p=0.574)
- Fan et al depression meta-analysis equivalent: in men, odds ratio=0.68, 95% confidence interval 0.32-1.47; and in women, odds ratio=1.40, 95% confidence interval 0.79-2.49
- Fan et al bipolar disorder meta-analysis equivalent: in men, odds ratio=0.90, 95% confidence interval 0.43-1.87; and in women, odds ratio=1.03, 95% confidence interval 0.63-1.66

Norton et al. (7-8-2002). Schizophrenia and functional polymorphisms in the MAOA and COMT genes: No evidence for association or epistasis. American Journal of Medical Genetics (Neuropsychiatric Genetics) 114(5): 491-496.
- Negative finding for MAOA 941T>G SNP (p=0.55), MAOA-3R & MAOA-5R (p=0.68), and COMT epistasis (p=0.43)

Grant et al. (1-24-2013). Dopaminergic foundations of schizotypy as measured by the German version of the Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE)—a suitable endophenotype of schizophrenia. Frontiers in Human Neuroscience 7(1): epub ahead of print.
- Higher cognitive disorganization (p=0.046) and introvertive anhedonia (p=0.016) in men with MAOA-3R
- Nonsignificant epistasis with COMT for unusual experiences

MAOA, Substance Use, & Addiction

Vanyukov et al. (4-24-1995). Preliminary evidence for an association of a dinucleotide repeat polymorphism at the MAOA gene with early onset alcoholism/substance abuse. American Journal of Medical Genetics 60(2): 122-126.

Hsu et al. (9-1-1996). Association of monoamine oxidase A alleles with alcoholism among male Chinese in Taiwan. American Journal of Psychiatry 153(9): 1209-1211.

Fowler et al. (11-26-1996). Brain monoamine oxidase A inhibition in cigarette smokers. PNAS 93(24): 14065-14069.
- Smoking lowers brain MAOA enzyme levels 28%, half of the effect of brief tranylcypromine treatment
- PET imaging

Gade et al. (1-1998). Correlation of length of VNTR alleles at the X-linked MAOA gene and phenotypic effect in Tourette syndrome and drug abuse. Molecular Psychiatry 3(1): 50-60.

Rossing. (5-1998). Genetic influences on smoking: Candidate genes. Environmental Health Perspectives 106(5): 231-238.

Berlin et al. (10-15-2009). Reduced monoamine oxidase A activity in pregnant smokers and in their newborns. Biological Psychiatry 66(8): 728-733.
- MAOA activity of births from smoking pregnant women measured by umbilical artery metabolites correlate with newborn facial twitching and grimaces

MAOA, BMI, & Diabetes

Camarena et al. (2004). Family-based association study between the monoamine oxidase A gene and obesity: Implications for psychopharmacogenetic studies. Neuropsychobiology 49(3): 126-129.

Need et al. (5-2006). Obesity is associated with genetic variants that alter dopamine availability. Annals of Human Genetics 70(3): 293-303.

Fuemmeler et al. (2-2008). Genes implicated in serotonergic and dopaminergic functioning predict BMI categories. Obesity 16(2): 348-355.
- National Longitudinal Study of Adolescent Health
- Male odds ratio 1.85, 95% confidence interval 1.18-2.94, p=0.04

Elgzyri et al. (7-2012). First-degree relatives of type 2 diabetic patients have reduced expression of genes involved in fatty acid metabolism in skeletal muscle. Journal of Clinical Endocrinology and Metabolism 97(7): E1332.
- Supplement

MAOA Cancer Research



MAOA in Popular Non-Fiction

Walsh, Anthony. Race and Crime: A Biosocial Analysis. Nova Science Publishers, Inc., 1-1-2004.

“Born to Rage?” National Geographic Explorer. National Geographic Channel. 12-14-2010.

“Born to Rage?” Dr. Phil. 4-4-2011.
- Falsely claimed “It’s estimated that a third of all men carry what’s been called the warrior gene.”
- Falsely claimed “… in the old days MAO inhibitors were used as antidepressants.” They are still used.
- Claimed that “… the genes give you the loaded pistol, and the environment is what pulls the trigger. You need to have both of those things to have the gun shoot.” This neglects the main effects of MAOA-2R and Brunner syndrome.
- Falsely claimed “It is more rare in women, of course.”

Pinker, Steven. The Better Angels of Our Nature: Why Violence Has Declined. New York: Viking Adult, 10-4-2011.
- Falsely claimed that “the racial disparity in American homicide has not always been with us.”
- Falsely claimed that “an association between the gene and aggression has not been found in non-European populations…” based on Widom and Brzustowicz.
- Falsely claimed that 70 percent of the Maori carry the low-activity version of MAOA
- Repeated the copy-and-paste error from Lea and Chambers, saying “the low-activity version of the gene is even more common in Chinese men (77 percent of whom carry it)…”

“How Evil are You?” Curiosity. Discovery Channel. 10-30-2011.

“The Warrior Gene?” Carte Blanche. M-Net. 10-7-2012.

Raine, Adrian. The Anatomy of Violence: The Biological Roots of Crime. Pantheon: New York, 4-30-2013.
- Falsely claimed that “[a]bout 30 percent of us have a variation in the MAOA gene that gives rise to relatively low levels of this enzyme…”
- Repeated the copy-and-paste error from Lea and Chambers, saying “[w]hile the base rate of the low-MAOA gene is about 34 percent in Caucasian males and 56 percent in the Maori, it is 77 percent in Chinese males.”
- Claimed that “It should be noted that the MAOA-antisocial relationship has not been found in all cultures. Shih and colleagues did not observe such a relationship with either antisocial personality disorder or antisocial alcoholism in participants from Taiwan…. Neither antisocial personality disorder nor antisocial alcoholism is associated with the MAO-A gene in Han Chinese males…. Furthermore, the interaction between abuse and low MAOA has not been found in African-Americans in one report: see Widom, C. S. & Brzustowicz, L. M. (2006).” Widom & Brzustowicz did not control for gender. Weder et al found the interaction in African Americans.