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

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.

Scientists Rediscover the Violence Gene, MAOA-2R

“It’s estimated that a third of all men carry what’s been called the warrior gene.”

— Dr. Phil

“There were three genes, as you mentioned. Call them violence genes. Call them bad-behavior genes. But what they found was that if people had these genes, they’re much more likely to be violent. There were certain triggers, as well: stress, family problems, low popularity, failing in school. To take it a step further, Karen, they sort of predict that about one percent of the population has these genes.”

— Dr. Sanjay Gupta, CNN

Both of these men are wrong, and both are referring to the same gene, monoamine oxidase A (MAOA). Roughly a third of white men inherit the 3-repeat allele of MAOA (MAOA-3R), which has received considerable research attention for influencing aggression. However, every other group, particularly African Americans, reach much higher allele frequencies, making MAOA-3R the most common version of the gene. Gupta was referring to a study of three potential violence-causing genes. One was the heterozygous pairing of ANKK1’s Taq1A allele (once thought to belong to DRD2), found in 37% of the subjects. Another was DAT1’s 10-repeat allele, found in 95% of the subjects. However, the strongest association with violence occurred in the third gene, MAOA, specifically the 2-repeat allele (MAOA-2R) found in that one percent that Gupta mentioned. I previously documented how this especially violent version of “the warrior gene” can be found much more commonly in African-American men than white or Asian men. Recently, an unusual study filled in some knowledge gaps about this highly understudied allele, specifically its effect on African-American men.

One unusual aspect of this study, Beaver et al, is that it essentially reexamined the exact same data as Guo et al, the study Gupta mentioned. The latter actually coincided with another study, also led by Guang Guo, on MAOA-2R in 2008 that determined that the allele doubles the rate of serious and violent delinquency. The impact most affected those aged twelve to fifteen, more than tripling the violent delinquency score based on eight questions. All three papers obtained their data from the National Longitudinal Study of Adolescent Health that totaled about 20,000 participants. However, only a seventh of that sample provided DNA, and Beaver et al focused on as few as eight black men for some of its findings.

That number might induce a healthy skepticism, but one should recall that this is not some newly discovered point mutation obtained in a “fishing expedition” bound for the annals of false positives. This gene produces an extremely important neurotransmitter enzyme that became the target of the first antidepressants in the 1950s. In the 1970s, studies linked its metabolites to aggression. In the late 80s, Hans Brunner discovered and became the eponym for a syndrome of violence resultant from complete deactivation of MAOA. His initial study included only five instances out of a family history of fourteen possible cases. Follow-up research increased the total subjects to nine from this single family. However, other researchers were able to induce Brunner syndrome in mice and eventually to discover such knockout-allele mice in a spontaneous form. Of course, a 2002 study instigated a tremendous amount of research on the gene-environment interaction, in which MAOA-3R coupled with the experience of child abuse triggers aggressive tendencies. The number of the “repeats” in the allele refers to the length of the more studied of the two promoters of the gene, and so those repeats can represent, to some extent, discrete levels of the enzyme’s dosage. In fact, the Guo et al 2008 study in the European Journal of Human Genetics included an in-vitro functional analysis of MAOA in human brain-tumor cells. MAOA-2R was less active than MAOA-3R, which was less active than MAOA-4R, the most common version in white people. MAOA-4R was more than three times as active as MAOA-2R.

I shall now briefly detail the sample characteristics that each of the three studies examined in order to ascertain how common MAOA-2R is in white and African-American men. Beaver et al claimed that the overall sample consisted of 2574 individuals, though Guo et al claimed a sample of 2524, including 1200 men. If Beaver et al was in error, then they have consistently repeated the error in other papers. In American Sociological Review, Guo et al only included 1111 men who met that study’s requirements, but both 2008 papers show that only eleven men had the 2R allele, and this study actually provided a racial breakdown of the sample: 60% white, 17% African American, 15% Hispanic American, and 8% Asian. The full genotyped Add Health male population is 57% white, which is 680 men. Beaver et al has listed 174 African-American men. Thus, nine black men by interviewer-assessed race (5.2%) or ten by self-reported race (5.5%) had the 2R allele. Beaver et al revealed that only 0.1% of white males had the 2R allele, which would equal just one man out of 680. That probably leaves none for Asians and Hispanics.

These numbers roughly correspond to other studies but suggest that I might have been too generous to African-American men in suggesting that they are only ten times more likely to have this especially dangerous version of MAOA. Reti et al previously genotyped a sample of 618 men and women who were 59% white and 38% African American. That study did not use a purely random sample. Seventy-five percent of that group received psychiatric evaluation within the Hopkins Epidemiology of Personality Disorders Study. That sample included 224 men and 391 women (with apparently three individuals missing possibly from rounding). Assuming both the black people and white people are 64% female, only three alleles out of 595 would have been 2-repeat alleles for white people. Eighteen of 377 would have been 2R for black people. Only about one white man out of possibly 133 would have been likely to have it, if even that, compared to four out of 85 black men. Likewise, Caspi et al in 2002 found one man with the 2R allele out of 499 white males. The trend seems to be that only a token white man in each study has this rare allele. Therefore, to say that the prevalence in whites is higher than Asians is sketchy. Since the new Beaver et al study uses a more random sample than Reti et al, and its white-male 2R prevalence is in closer agreement with Caspi et al than Reti et al, I suspect that this allele is closer to 50 times more common in black men than white men rather than 10 times, as I previously wrote.

Most research on MAOA compares MAOA-3R to MAOA-4R in white males with token instances of MAOA-2R thrown in with MAOA-3R under the label “MAOA-L.” So, these studies are made more shocking by the lumping of “the warrior gene,” MAOA-3R, together with the high-activity allele, MAOA-4R, as the non-violent versions of the gene. The astounding results speak for themselves. Beaver et al found that the ten black men who possessed MAOA-2R had triple the risk of incarceration and almost quadruple their risk of arrest, (accounting for 8.6% of the arrested and 9.5% of the incarcerated). A sample of only eight black men with MAOA-2R out of 130 black men had a statistically significant increased risk of self-reported violence. Scientists have tried to ameliorate the politically unpalatable nature of violence-gene research by emphasizing the environmental trigger for aggression with MAOA-3R, but the findings of Beaver et al and Guo et al did not depend on any environmental trigger. Beaver et al asserted that “the low base-rate of 2-repeat allele carriers prevented an exploration of gene-environment interaction…” However, Guo et al went right ahead and also tested for an interaction between MAOA-2R and being held back a grade in school and three questions regarding feelings of school attachment. The gene’s interaction increased violent delinquency 21 times as much as grade retention alone and seven times as much as school attachment alone.

Given that the men with MAOA-2R in the National Longitudinal Study of Adolescent Health are ten African Americans and one white, I doubt the effectiveness of the regression analysis adjustment for race and ethnicity claimed by Guo et al. Put another way, 91% of the exposed cohort come from a racial group that is 13% of all Americans. Their studies should have laid bare this fact. Beaver et al limited their analysis to the black men, but even that raises concerns of population stratification because African Americans are a mixed population, averaging 22% European ancestry. Africa, itself, has produced no MAOA research, (but it did copy a sensational National Geographic documentary on MAOA). If MAOA-2R is so closely associated with African ancestry, then it could serve as a proxy for having more African alleles. Of course, this logic never stopped any of the other research on African Americans, and the implication that multiple other African violence alleles confound this association does not fit the mold of politically correct impugnment usually directed at MAOA research.



Part of my fascination with the sparse research on MAOA-2R comes from my belief that scientists have inadvertently underplayed the true power of this gene. Comparing the two most common versions of MAOA requires less effort and funding, and emphasizing an environmental trigger, like child abuse, varnishes genetics research with a politically correct gloss. However, the trigger for MAOA-3R quickly multiplied to include testosterone levels, maternal smoking, IQ, education, and socio-economic status. Some of those “environmental” factors actually have a dominant hereditary influence. Now, studies have triggered aggression in MAOA-3R men with much more immediate experimental adversities in the form of game unfairness. Furthermore, people like Dr. Phil assume that a gene-environment interaction is synonymous with a “genetic predisposition,” but the “non-active” allele actually appears to play a protective role that negates an environmental trigger’s impact. For instance, low IQ does not increase violent tendencies in men with MAOA-4R, but it does in men with MAOA-3R.

Incidentally, Steven Pinker’s latest book addressed the Flynn Effect. “If smarter people and smarter societies are less likely to be violent, then perhaps the recent rise in intelligence can help explain the recent decline of violence.” However, a hypothesis of much longer-term IQ decline has recently ridden a wave of genetic-load angst, so allow me to point out the tension between these competing paradigms as a challenge to Pinker’s broader thesis. The complex associations between intelligence, executive function, and aggression might have also drawn in olfaction research. Both judgment and the ability to discern smells localize to the frontal lobes, and research has linked poor olfactory acuity to aggression. As with MAOA allele frequencies, racial disparities exist for odor identification.

Since Brunner syndrome and MAOA-2R seem to have a “main effect” without an environmental trigger, I see the MAOA-3R gene-environment interaction as a penumbra of the possible enzymatic effects. In an entire population, the prevalence of violence must have a specific total MAOA component that would consist of all of the MAOA variants (including potential epigenetic effects, SNPs, and both VNTR promoters, only one of which is the subject of most “warrior gene” research) and each variant’s potential when unlocked by all possible environmental triggers. Even with enormous samples, whole-genome studies are capable of studying a tiny fraction of this genetic potential. Similarly, quantitative genetics research, like twins studies, underestimates heritability when some large genetic effects are unlocked by environmental stimuli, as opposed to a merely additive nature-nurture relationship. Terrie Moffitt and Avshalom Caspi, who spearheaded early gene-environment research, wrote an extended analysis of this approach with Michael Rutter. “For understanding the influence of such conditional-effect genes, large samples may be less necessary than strategic [gene-environment interaction] research.”

Rather than use the penumbra of gene-environment interactions to appreciate the extensiveness of a gene’s effect, scientists like Moffitt, Caspi, and Rutter seek to dispel genetic “determinism.” Citing a two-hour student protest of a scientific conference on the genetics of violence, they explained, “Ethicists attribute the root of the public’s concern about genes to a pervasive belief in the power of genetic determinism: ‘ … genetic determinism implies that knowing a person’s genetic makeup is tantamount to knowing his or her future.’” If the public detests genetic determinism due to its unyielding quality, then surely such people would rather seek methods to circumnavigate genetic fate than to simply disacknowledge the power of heredity. However, Moffitt et al wish for the opposite: “Concrete data needed to counter genetic determinism are provided by new [gene-environment interaction] findings…. Such understanding should make eugenics and other misuses of genetic information much more difficult.” This discussion calls for a debate over both the feasibility and the ethics of changes to environmental triggers, like poverty, versus those of the ill-defined “misuses” of genetic knowledge. Presumably hypothetical therapeutic drugs and diagnostic tests for violent tendencies would not necessarily misuse the research, and the solutions to poverty and educational failure are not just around the corner.

Obviously, many scientists and activists who oppose genetic determinism believe in a greater role for nurture or even blank-slate nurture determinism, but they wish to leverage the masses, who ascribe behavior to supernatural “free will.” To qualify as deterministic, must genetic aggressivity present itself constantly? Though MAOA has no activity in Brunner syndrome, the subjects need not reside in cages, gnawing on the bars. Most men with the MAOA knockout allele are afflicted with conduct disorder and “conflict with the law” during their lifetime. A provocation of some sort might set off aggression, but minor provocations exist in the lives of all people, so Brunner syndrome should still qualify as deterministic. Whether the existence of such determinism is “nice” or not has no bearing on its existence, so do not mistake denial for virtue.

Wickedpedia
I might have missed the recent Beaver et al study, if others had not pointed it out to me. Unlike most MAOA research, it did not surface in the PubMed database. I think that is true of all studies from the Journal of Personality and Individual Differences of the London School of Differential Psychology. Some of the journal’s board members, including recently deceased Arthur Jensen, received the label “scientific racist” from certain activists. So, Kevin Beaver refused to submit to an interview for this blog, but he saw fit to publish in a journal that recently reviewed research on penis length and circumference differences among “Negroids,” “Caucasoids,” and “Mongoloids.” A year ago, I was able to send him a list of questions, in which I confronted him for conflating MAOA-2R and MAOA-3R as “MAOA-L.” He told me that a study on MAOA-2R was “in the pipeline.” However, I would like to think that I inspired the study, and I find it jarring that four years could pass without any research on MAOA-2R and violence.

Is anyone following this research as well as I am? Many professions fight “turf wars.” This occurs among medical professionals and physician specialties. Study of MAOA and violence likens less to competition over a lucrative procedure and more to a game of “hot potato.” Violence, itself, does not have a dedicated category in the Diagnostic and Statistical Manual of Mental Disorders. Though psychiatrists have contributed some research, it seems that psychologists and criminologists like Beaver have taken the lead usually with low-cost data mining from databases like the National Longitudinal Study of Adolescent Health.

Meanwhile, public attention to the gene increasingly falls to self-appointed experts and “ethicists,” who cannot even report some very basic facts about the gene correctly. Pseudointellectuals are claiming that “most if not all of this literature [on MAOA] is wrong, and [sic] will soon be forgotten” and that a “single molecule” like serotonin or dopamine cannot explain “complex behavior.” When Scientologists mouth these stupid ideas, most people roll their eyes, but now the same ideas are coming from “science reporters” and Harvard professors. Therefore, I decided to take the drastic measure of addressing what I think might be the source of the problem by editing Wikipedia. Before I started editing the Wikipedia pages for Brunner syndrome and MAOA, activists had peppered them with qualifications that the evidence was “flawed” or “controversial” or that the emerging field of epigenetics made the gene’s effects “hard to predict.” Apparently, methyl moieties escape the rule that a single type of molecule cannot determine a complex behavior. Never mind studies that show the epigenetics of MAOA in men is minimal, low in variance, and high in hereditary influence. Of course, it is never enough to simply edit a fix into a Wikipedia page. First, one makes the edit. Then, one reapplies the edit repeatedly after activists try to undo one’s work. Finally, one replies to the activist on one’s personal “talk” page when the activist threatens to undo one’s work again unless one attaches to an email the study that proves the activist’s sacred belief is based on a copy-and-paste error. A stronger commitment predicates some Wikipedia myths than that of many a marriage.

Some are rightfully criticizing this research and candidate-gene behavioral genetics, in general, because small sample sizes can cause false positives by measure of statistical significance. However, since no other approach is capable of studying VNTRs like MAOA, the only current solution would be to fund the research more rather than to advocate censorship of the research that is being done. Rarely do I hear similar criticism of functional magnetic resonance imaging (fMRI) research, which tends to have small samples due to the expense of the imaging but makes up for it with pretty color explosions on brain maps. When I worked with fMRI, I thought that the arbitrary threshold settings that defined the “areas of increased activity” added an extra layer of bias. Perhaps the Harvard establishment has singled out behavioral genetics for rebuke in order to centralize the potential for offensive findings and to avoid “misuse.”

Congratulations! You Have Cancer!
The study of MAOA has received a beautiful gift—the gift of cancer. One might recall the fad cureall and supplier of immortality known as antioxidants. Antioxidants are supposed to save cells by counteracting free radicals. However, too much of a good thing like cell survival is cancer. MAOA deserves to be called the “warrior gene” because it makes oxidases that slay cancer cells. Malorni et al first discovered this in 1998 when the MAOA-inhibiting drug, clorgyline, saved melanoma cells, in vitro. Ten years later, Alpini et al concluded that epigenetic effects on the MAOA VNTR could explain its lower enzyme levels in cholangiocarcinoma, cancer of the liver bile ducts. Now, Huang et al has determined that higher MAOA expression decreased the risk of metastasis and improved prognosis and survival in patients with cholangiocarcinoma. Though the decline in MAOA expression seemed mostly limited to the areas of malignancy, I have found some online family-member portrayals of men with the disease becoming “distant,” “difficult,” “angry,” “grumpy,” “horrible,” and “mean,” in some cases prior to diagnosis.

This calls for drugs that increase MAOA levels, and maybe the resulting therapies could metastasize to psychiatric uses. A few contestants already have records of accomplishment. Doctors sometimes use risperidone, an older-generation antipsychotic, to treat impulsive aggression. In fact, Tuinier et al detailed a case report of a Brunner syndrome patient who successfully responded for a time to risperidone. Nevertheless, the drug has serious adverse reactions, causing many patients to gain weight, and a small percentage develop permanent tardive dyskinesia, involuntary movements often of the lips. Tetrabenazine and ketanserin reduced aggression in MAOA-knockout mice. Tetrabenazine is used to treat chorea, the involuntary movements of Huntington’s disease. The FDA granted it official orphan-drug status in 2008, but it is incredibly expensive for Americans to use. Ketanserin has applications for high blood pressure, but it is unavailable in the US.

Maybe this cancer research could save MAOA from its “controversial” reputation. Harvard professors might hesitate to dismiss a violence gene that became a cancer gene. After all, lives are at stake.










Alpini G, Invernizzi P, Gaudio E, Venter J, Kopriva S, Bernuzzi F, Onori P, Franchitto A, Coufal M, Frampton G, Alvaro D, Lee SP, Marzioni M, Benedetti A, & DeMorrow S (2008). Serotonin metabolism is dysregulated in cholangiocarcinoma, which has implications for tumor growth. Cancer research, 68 (22), 9184-93 PMID: 19010890

Beaver, K., Wright, J., Boutwell, B., Barnes, J., DeLisi, M., & Vaughn, M. (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 DOI: 10.1016/j.paid.2012.08.014

Brunner HG, Nelen MR, van Zandvoort P, Abeling NG, van Gennip AH, Wolters EC, Kuiper MA, Ropers HH, & van Oost BA (1993). X-linked borderline mental retardation with prominent behavioral disturbance: phenotype, genetic localization, and evidence for disturbed monoamine metabolism. American journal of human genetics, 52 (6), 1032-9 PMID: 8503438

Cases O, Seif I, Grimsby J, Gaspar P, Chen K, Pournin S, Müller U, Aguet M, Babinet C, & Shih JC (1995). Aggressive behavior and altered amounts of brain serotonin and norepinephrine in mice lacking MAOA. Science (New York, N.Y.), 268 (5218), 1763-6 PMID: 7792602

Caspi A, McClay J, Moffitt TE, Mill J, Martin J, Craig IW, Taylor A, & Poulton R (2002). Role of genotype in the cycle of violence in maltreated children. Science (New York, N.Y.), 297 (5582), 851-4 PMID: 12161658

Crabtree, G. (2013). Our fragile intellect. Part II Trends in Genetics, 29 (1), 3-5 DOI: 10.1016/j.tig.2012.10.003

Fergusson DM, Boden JM, Horwood LJ, Miller A, & Kennedy MA (2012). Moderating role of the MAOA genotype in antisocial behaviour. The British journal of psychiatry : the journal of mental science, 200 (2), 116-23 PMID: 22297589

Gallardo-Pujol D, Andrés-Pueyo A, & Maydeu-Olivares A (2012). MAOA genotype, social exclusion and aggression: an experimental test of a gene-environment interaction. Genes, brain, and behavior PMID: 23067570

Guo, G., Roettger, M., & Cai, T. (2008). The Integration of Genetic Propensities into Social-Control Models of Delinquency and Violence among Male Youths American Sociological Review, 73 (4), 543-568 DOI: 10.1177/000312240807300402

Guo, G., Ou, X., Roettger, M., & Shih, J. (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 DOI: 10.1038/sj.ejhg.5201999

Huang L, Frampton G, Rao A, Zhang KS, Chen W, Lai JM, Yin XY, Walker K, Culbreath B, Leyva-Illades D, Quinn M, McMillin M, Bradley M, Liang LJ, & DeMorrow S (2012). Monoamine oxidase A expression is suppressed in human cholangiocarcinoma via coordinated epigenetic and IL-6-driven events. Laboratory investigation; a journal of technical methods and pathology, 92 (10), 1451-60 PMID: 22906985

Jones, R., Brown, C., & Ship, J. (1995). Odor identification in young and elderly African-Americans and Caucasians Special Care in Dentistry, 15 (4), 138-143 DOI: 10.1111/j.1754-4505.1995.tb00501.x

Mahmut, M., & Stevenson, R. (2012). Olfactory Abilities and Psychopathy: Higher Psychopathy Scores Are Associated with Poorer Odor Discrimination and Identification Chemosensory Perception, 5 (3-4), 300-307 DOI: 10.1007/s12078-012-9135-7

Malorni W, Giammarioli AM, Matarrese P, Pietrangeli P, Agostinelli E, Ciaccio A, Grassilli E, & Mondovi B (1998). Protection against apoptosis by monoamine oxidase A inhibitors. FEBS letters, 426 (1), 155-9 PMID: 9598998

McDermott R, Tingley D, Cowden J, Frazzetto G, & Johnson DD (2009). Monoamine oxidase A gene (MAOA) predicts behavioral aggression following provocation. Proceedings of the National Academy of Sciences of the United States of America, 106 (7), 2118-23 PMID: 19168625

Moffitt, T., Caspi, A., & Rutter, M. (2006). Measured Gene-Environment Interactions in Psychopathology. Concepts, Research Strategies, and Implications for Research, Intervention, and Public Understanding of Genetics Perspectives on Psychological Science, 1 (1), 5-27 DOI: 10.1111/j.1745-6916.2006.00002.x

Murphy SM, Puwanant A, Griggs RC, & Consortium for Clinical Investigations of Neurological Channelopathies (CINCH) and Inherited Neuropathies Consortium (INC) Consortia of the Rare Disease Clinical Research Network (2012). Unintended effects of orphan product designation for rare neurological diseases. Annals of neurology, 72 (4), 481-90 PMID: 23109143

Pietrangeli, P. (2004). Amine Oxidases and Tumors NeuroToxicology, 25 (1-2), 317-324 DOI: 10.1016/S0161-813X(03)00109-8

Reti IM, Xu JZ, Yanofski J, McKibben J, Uhart M, Cheng YJ, Zandi P, Bienvenu OJ, Samuels J, Willour V, Kasch-Semenza L, Costa P, Bandeen-Roche K, Eaton WW, & Nestadt G (2011). Monoamine oxidase A regulates antisocial personality in whites with no history of physical abuse. Comprehensive psychiatry, 52 (2), 188-94 PMID: 21295226

Roush, W. (1995). Conflict marks crime conference Science, 269 (5232), 1808-1809 DOI: 10.1126/science.7569909

Scott, A., Bortolato, M., Chen, K., & Shih, J. (2008). Novel monoamine oxidase A knock out mice with human-like spontaneous mutation NeuroReport, 19 (7), 739-743 DOI: 10.1097/WNR.0b013e3282fd6e88

Shih JC, Ridd MJ, Chen K, Meehan WP, Kung MP, Seif I, & De Maeyer E (1999). Ketanserin and tetrabenazine abolish aggression in mice lacking monoamine oxidase A. Brain research, 835 (2), 104-12 PMID: 10415365

Sjöberg, R., Ducci, F., Barr, C., Newman, T., Dell'Osso, L., Virkkunen, M., & Goldman, D. (2007). A Non-Additive Interaction of a Functional MAO-A VNTR and Testosterone Predicts Antisocial Behavior Neuropsychopharmacology, 33 (2), 425-430 DOI: 10.1038/sj.npp.1301417

Tuinier S, Verhoeven WMA, Scherders MJWT, Fekkes D, & Pepplinkhuizen L (1995). Neuropsychiatric and biological characteristics of X-linked MAOA deficiency syndrome: A single-intervention case study. New Trends in Experimental and Clinical Psychiatry, 11 (4), 99-107

Wong CC, Caspi A, Williams B, Craig IW, Houts R, Ambler A, Moffitt TE, & Mill J (2010). A longitudinal study of epigenetic variation in twins. Epigenetics : official journal of the DNA Methylation Society, 5 (6), 516-26 PMID: 20505345

Kill Popular Science

Steven Pinker’s new book, “The Better Angels of Our Nature,” is out, and the reception reminds me of an album release from a trendy band during the 1990’s. I must beg my readers’ forgiveness for writing this very preliminary review for a book that I have not finished because the subject matter is so important. Most reviews and buzz for this book center on Pinker’s observations about the decline of violence and the advance of enlightened views. Pinker has been speaking about this phenomenon for years, and many facets of it are apparent in my own lifetime, such as the utter metamorphosis of public consensus regarding homosexuality. The book has a number of fascinating graphs that speak to the changes, and I have little reason to critique his central thesis, other than to say that I am not sure the trend entirely represents genuine progress. For example, I suspect that he could have placed a graph of the decline of fat jokes alongside his graphs of the decline of racial prejudices. While society has improved control over physical aggression, the obesity epidemic proves that indiscipline still finds expression. In fact, when one considers the growing acceptance of “alternative”—excuse me, “integrative” medicine, one can see how the triumph of enlightened tolerance can coincide with a lax shrug off of reason and scientific rigor.

Though I perused the tome in the modern cursory version of the word’s contradictory meanings, I gave special attention to the latter chapters, particularly chapters 8 and 9 on the nature of violence, itself, which has been one of my obsessions. That discussion concerns the overriding paradox of this work. How could this man, who wrote The Blank Slate to passionately declare that we are not and that behavior is part heredity, reconcile with a belief that societal evolution pushed radical behavioral modification? I regret to say that this was a serious weakness of an otherwise well-reasoned exposition.

First let me stress that I do not see Pinker’s observations as fundamentally opposed to the revolution taking place in biosocial criminology and genetic psychiatry. On the contrary, making aggression anomalous likely accentuates the role of genetics and biology in what deserves to be considered a veritable behavioral disease. What science really calls into question is whether historic trends justify extrapolation, and from what I can tell, Pinker has dodged such speculation. To illustrate his handling, the book contains extensive discussion of how the secular rise in IQ, known as the Flynn effect, could be reducing violence, but I found no mention of the evidence for subsequent plateauing. Then again, my hope is that the research on the genetics of violence, which I attempt to elucidate, could help channel efforts to find new ways, including pharmacological developments, to sustain aggression’s decline.

Judging by Pinker’s treatment of the subject, my message is not getting out. He dismissed research on monoamine oxidase A (MAOA) using a study with which my regular readers are all too familiar.

[A]n association between the gene and aggression has not been found in non-European populations, perhaps because they have evolved other ways of regulating their catecholamine levels. (Genes often act in networks regulated by feedback loops, so in populations in which a particular gene is less effective, other genes may step up their activity to compensate.) For now, the Warrior Gene theory is staggering around with possibly fatal wounds.

Nice try. Pinker is referencing the Widom and Brzustowicz paper that combined men and women to compare “whites” to “non-whites.” Gender was not controlled, and that white sample was 33% female. Non-whites were 38% female, but women were far more represented among non-white subjects with the low-activity, 3-repeat allele. For the subjects with the 3-repeat allele, which is the allele considered most impacted by the environmental trigger, whites were 24% female, and non-whites were 43% female. Antisocial behavior in women, but not men, is mediated by the epigenetic methylation of MAOA as well as a newly discovered second promoter that actually has more effect in women than the alleles mentioned. Also, of course, MAOA is located on the X chromosome. Women have two copies, which helps explain why even the radical Brunner-syndrome mutation that completely disables the gene does not seem to affect the behavior of women. It can be nice to have a spare.

Pinker seems to have received his introduction to this subject through the New Zealand Maori controversy, in which Rod Lea had to make amends for allegedly saying that the Maori are prone to criminality. Thus, Pinker is completely unaware that studies have found that MAOA influences aggression in non-whites. Weder et al found that the gene-environment association of MAOA and aggression held for a 58-subject sample of African-American and biracial children. Kevin Beaver’s research also helps support this association. His 2009 study on MAOA’s effect on gang membership and weapon use included African Americans. His 2010 study on African-American men and violence used a genetic index that included MAOA and four other genes that affect catecholamine levels.

At least claiming that MAOA does not affect non-white people fits a politically correct agenda of raising the self-esteem of minorities who feel the burden of a violent stereotype. What would you think of Steven Pinker if he spread a complete falsehood that could label a group of people genetically violent without any scientific basis whatsoever?

[T]he low-activity version of the gene is even more common in Chinese men (77 percent of whom carry it), and the Chinese are neither descended from warriors in their recent history nor particularly prone to social pathology in modern societies.

I previously debunked this, but I guess I must do so, again. A study by Lu et al found that 42 Taiwanese men, or 55% of their 77-subject control sample, had the 3-repeat allele of MAOA. Lea and Chambers copied the information incorrectly. Then, an editorial against MAOA research by a doctoral student repeated the falsehood. Now, Pinker has immortalized this slander against Chinese people in a bestselling book. The actual allele frequency given by Lu et al matches the allele frequency found for Asians in subsequent research, which is not higher than that of other groups besides white people. Pinker, like so many others, conflated the 3-repeat allele with the 2-repeat allele as the “low-activity allele,” even though the 2-repeat allele doubles the association with violence without needing an environmental trigger. The 2-repeat allele accounts for 4.7% of African-American MAOA genes and 0.00067% of Asian MAOA genes (assuming that the only Chinese control subject with the allele did not have mixed ancestry). Not only does this bogus insult create a new stereotype for Chinese people, but the numbers error reinforces an old generalization, as all four guilty parties were white boys. (Chinese people, when you buy my neighborhood, recall that I personally sent Pinker a corrigendum request.)


Herein lies the problem with popular science. Steven Pinker is a Harvard professor who previously chastised Malcolm Gladwell for misspelling “igon value.” Pinker’s new book encompasses a prodigious collection of disparate lines of evidence. Even so, he dismissed a vital segment of potentially life-saving research using biased sources that were motivated at least in one case by racial politics. When Dr. Phil stumbled through his television show episode on the warrior gene, he made mistakes and showed his ignorance, but he did not bring an entire field of study into disrepute. However, when Malcolm Gladwell or Stephen Jay Gould call IQ testing an “ice flow” or decry its “reification,” it has consequences for science. Gladwell and Pinker inhabit a pantheon of respected liberal thinkers whose influence reverberates throughout academia. Their stature alone can transform an ignorant statement into an authoritative observation. Their superficial summations can leave a lasting imprint on another’s life’s work, as they bring along a vast audience of comparative ignoramuses to boo rogue points of view (not unlike a daytime talk show).









Widom CS, & Brzustowicz LM (2006). MAOA and the "cycle of violence:" childhood abuse and neglect, MAOA genotype, and risk for violent and antisocial behavior. Biological psychiatry, 60 (7), 684-9 PMID: 16814261

Weder N, Yang BZ, Douglas-Palumberi H, Massey J, Krystal JH, Gelernter J, & Kaufman J (2009). MAOA genotype, maltreatment, and aggressive behavior: the changing impact of genotype at varying levels of trauma. Biological psychiatry, 65 (5), 417-24 PMID: 18996506

Beaver KM, DeLisi M, Vaughn MG, & Barnes JC (2010). Monoamine oxidase A genotype is associated with gang membership and weapon use. Comprehensive psychiatry, 51 (2), 130-4 PMID: 20152292

Kevin Beaver, Ashley Sak, Jamie Vaske, & Jessica Nilsson (2010). Genetic risk, parent–child relations, and antisocial phenotypes in a sample of African-American males Psychiatry Research, 175 (1-2), 160-164

Lu RB, Lee JF, Ko HC, Lin WW, Chen K, & Shih JC (2002). No association of the MAOA gene with alcoholism among Han Chinese males in Taiwan. Progress in neuro-psychopharmacology & biological psychiatry, 26 (3), 457-61 PMID: 11999895

Lea R, & Chambers G (2007). Monoamine oxidase, addiction, and the "warrior" gene hypothesis. The New Zealand medical journal, 120 (1250) PMID: 17339897

Patrick-Michael Whittle (2009). Darwinism and the nature of Māori MAI Review

Philibert RA, Gunter TD, Beach SR, Brody GH, & Madan A (2008). MAOA methylation is associated with nicotine and alcohol dependence in women. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, 147B (5), 565-70 PMID: 18454435

Philibert RA, Wernett P, Plume J, Packer H, Brody GH, & Beach SR (2011). Gene environment interactions with a novel variable Monoamine Oxidase A transcriptional enhancer are associated with antisocial personality disorder. Biological psychology, 87 (3), 366-71 PMID: 21554924

Attack of the Warrior Gene Babies!

The so-called “warrior gene” is the reason babies have tantrums. And you thought it was creamed spinach. Okay, I lied. Actually, the first study on the effects of monoamine oxidase A (MAOA) on infants determined that the 3-repeat allele decreases behavioral regulation in Chinese baby girls. Crying was a controlled factor because it could represent fear rather than baby rage. Behavioral regulation was measured by gaze aversion from a menacing toy gorilla. Believe it or not, the inability to do this is associated with childhood externalizing behaviors like fighting and hitting.

The only significant main effect of MAOA was in the girls, which was fodder for interesting discussion of the gender differences and developmental component of the gene’s expression. MAOA is subject to epigenetic methylation, but mostly just in women. The vast majority of that methylation seems to have already occurred by age 5, according to Wong et al. Increased methylation gives women more symptoms of alcohol and nicotine dependence but not antisocial personality disorder, according to Philibert et al. The warrior gene concerns a VNTR (variable number tandem repeat) promoter, but another study by Philibert et al recently discovered a second VNTR that seems to have a greater effect on antisocial personality disorder in women (but not men) than the heavily studied VNTR, and both VNTR influence MAOA methylation in women. The fact that the sex hormones testosterone and estradiol affect MAOA expression should also enter any thorough discussion of sex differences in the warrior gene. Such increasingly complex factors involved in MAOA expression in women are modifying a long-held view that MAOA does not affect women even when it is completely shut off in Brunner syndrome. Or as Dr. Phil put it, “[the warrior gene] is more rare in women, of course” which is not actually true, but at least he is trying.

Speaking of hormones, over the past decade many studies have examined the effects of testosterone and cortisol on aggression. One study determined that testosterone and cortisol even affect the militancy and aggression of Palestinians. Oddly, this research has never seemed to cross paths with research on the proven effects of testosterone and cortisol on MAOA expression. However, scientists have identified a gene-gene interaction between the androgen receptor and glucocorticoid receptor genes, so these might be violence genes just like MAOA, DAT1, DRD2, DRD4, and 5-HTTLPR.

Getting back to the study on babies, this new data also helps clarify the allele frequencies in Asians. I now count a nearly 1,500 cumulative allele sample size among those Asian subjects, predominantly Chinese, for whom selection bias does not apply, and 54% are the warrior gene, which I consider the three-repeat allele (although the much less common 2-repeat allele is also included under this label). This is not much different from that of African Americans, but nearly five percent of African American men have the more violent 2-repeat allele, compared to only one allele of Asian control subjects in the seven studies that I counted. A 2009 editorial that was included in a series of attacks on MAOA research as a reaction to the Rod Lea/Maori controversy claimed Chinese people have the highest warrior gene allele frequency of any ethnic group. That was based on an uncorrected error in The New Zealand Medical Journal that switched the number of subjects (77) with the percentage with the three-repeat allele (55%) from the study by Lu et al. One would think that researchers who study warriors would be more careful.






Zhang M, Chen X, Way N, Yoshikawa H, Deng H, Ke X, Yu W, Chen P, He C, Chi X, & Lu Z (2011). The association between infants' self-regulatory behavior and MAOA gene polymorphism. Developmental science, 14 (5), 1059-1065 PMID: 21884321

Zhou Q, Hofer C, Eisenberg N, Reiser M, Spinrad TL, & Fabes RA (2007). The developmental trajectories of attention focusing, attentional and behavioral persistence, and externalizing problems during school-age years. Developmental psychology, 43 (2), 369-85 PMID: 17352545

Wong CC, Caspi A, Williams B, Craig IW, Houts R, Ambler A, Moffitt TE, & Mill J (2010). A longitudinal study of epigenetic variation in twins. Epigenetics : official journal of the DNA Methylation Society, 5 (6), 516-26 PMID: 20505345

Philibert RA, Gunter TD, Beach SR, Brody GH, & Madan A (2008). MAOA methylation is associated with nicotine and alcohol dependence in women. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, 147B (5), 565-70 PMID: 18454435

Philibert RA, Wernett P, Plume J, Packer H, Brody GH, & Beach SR (2011). Gene environment interactions with a novel variable Monoamine Oxidase A transcriptional enhancer are associated with antisocial personality disorder. Biological psychology, 87 (3), 366-71 PMID: 21554924

Victoroff J, Quota S, Adelman JR, Celinska B, Stern N, Wilcox R, & Sapolsky RM (2011). Support for religio-political aggression among teenaged boys in Gaza: part II: neuroendocrinological findings. Aggressive behavior, 37 (2), 121-32 PMID: 21274850

Chen S, Wang J, Yu G, Liu W, & Pearce D (1997). Androgen and glucocorticoid receptor heterodimer formation. A possible mechanism for mutual inhibition of transcriptional activity. The Journal of biological chemistry, 272 (22), 14087-92 PMID: 9162033

Sue Z. Sabol, Stella Hu, & Dean Hamer (1998). A functional polymorphism in the monoamine oxidase A gene promoter Human Genetics, 103 (3), 273-279 : 10.1007/s004390050816

Ono H, Shirakawa O, Nishiguchi N, Nishimura A, Nushida H, Ueno Y, & Maeda K (2002). No evidence of an association between a functional monoamine oxidase a gene polymorphism and completed suicides. American journal of medical genetics, 114 (3), 340-2 PMID: 11920860

Lu RB, Lee JF, Ko HC, Lin WW, Chen K, & Shih JC (2002). No association of the MAOA gene with alcoholism among Han Chinese males in Taiwan. Progress in neuro-psychopharmacology & biological psychiatry, 26 (3), 457-61 PMID: 11999895

Rosenberg S, Templeton AR, Feigin PD, Lancet D, Beckmann JS, Selig S, Hamer DH, & Skorecki K (2006). The association of DNA sequence variation at the MAOA genetic locus with quantitative behavioural traits in normal males. Human genetics, 120 (4), 447-59 PMID: 16896926

Wang TJ, Huang SY, Lin WW, Lo HY, Wu PL, Wang YS, Wu YS, Ko HC, Shih JC, & Lu RB (2007). Possible interaction between MAOA and DRD2 genes associated with antisocial alcoholism among Han Chinese men in Taiwan. Progress in neuro-psychopharmacology & biological psychiatry, 31 (1), 108-14 PMID: 17007976

Lee SY, Hahn CY, Lee JF, Huang SY, Chen SL, Kuo PH, Lee IH, Yeh TL, Yang YK, Chen SH, Ko HC, & Lu RB (2010). MAOA interacts with the ALDH2 gene in anxiety-depression alcohol dependence. Alcoholism, clinical and experimental research, 34 (7), 1212-8 PMID: 20477771

Patrick-Michael Whittle (2009). Darwinism and the nature of Māori MAI Review

Lea R, & Chambers G (2007). Monoamine oxidase, addiction, and the "warrior" gene hypothesis. The New Zealand medical journal, 120 (1250) PMID: 17339897