The Alondra Oubré Academic Fraud Exposed

Alondra Oubré Wikipedia Scholar

As further proof that a specific violence gene common to Africans threatens the worldview of fundamentalist anthropologists, Wikipedia scholar Alondra Oubré became the latest anthropologist to post an error-riddled Internet screed against the warrior gene, monoamine oxidase A (MAOA). Oubré is the author of Instinct and Revelation: Reflections on the Origins of Numinous Perception and Race, Genes and Ability: Rethinking Ethnic Differences. She is also an expert at copying errors from Wikipedia into her writing. Her *Wikipedia* page lists her as a “newsmaker,” “prominent African American,” and an “African American achiever.” As an anti-science anthropologist, she joined her colleagues in writing another editorial against Nicholas Wade’s recent book, A Troublesome Inheritance, as well as the study of MAOA, a gene verified as causing violence in multiple meta-analyses. Unlike previous attacks on this science, no possibility exists that this is anything other than academic fraud. Oubré took false information from Wikipedia, for which I provide here the proof, and she deliberately lied about her source. I repeatedly requested an official correction from her editor, author and City University of New York professor Massimo Pigliucci, who refused to do so. What follows is a point-by-point refutation of Oubré’s work.

Wow! What a poorly researched Internet post! I hope you don’t mind if I post the factual corrections here for you.

“The most common variant, MAOA-4R, has four repeats and is associated with high-activity breakdown of neurotransmitters.”

I guess it would be true that MAOA-4R is the most common variant if everyone in the world was white.

“Up to this point, all of the studies on the MAOA gene had been conducted in Caucasians. That changed when researchers started investigating this gene in the Maori of New Zealand.”

No, here is a list of studies that looked at non-whites prior to that study: Sabol et al, Kunugi et al, Balciuniene et al, Gilad et al, Ono et al, Williams et al, Koen et al, Huang et al, Yu et al, Young et al, Widom & Brzustowicz, and Rosenberg et al.

“For many experts, this ethnic gap is the result of numerous environmental causes, including poverty.”

I think you should revise this sentence.

“It turned out that while 3R was found in 56% of Maori males, it occurred in 58% of African American males and 34% of European males.”

Notice how the African-American number is slightly lower than the source? Someone in Wikipedia has been tweaking the numbers at will. I don’t recommend that you rely so heavily on Wikipedia as your source for just this sort of reason. I also don’t recommend that you rely on that “study” by Lea and Chambers, which was the source of the “idiot test” copy-and-paste error that slandered Chinese men as having an MAOA-3R allele frequency of 77%.

“Interestingly, the press ignored studies indicating that the 3R variant occurred in 61% of Taiwanese males [15] and 56% of Chinese males [16].”

You switched your sources. Both samples were Taiwanese. You rounded 54.5% to 56%. That’s kind of sloppy.

“In the Add Health database, 5.5% of African American men, 0.9% of Caucasian men, and 0.00067% of Asian men have 2R.”

So, you took these numbers from Add Health, did you? No, you didn’t. I know because I calculated the number for Asian men and posted it on my blog and Wikipedia. Once again, the Wikipedia troll screwed up your numbers for white men by a factor of 9. The Asian allele frequency was based on eight studies. I only found one Asian with MAOA-2R in those studies, but I have since looked at other studies and revised the number upwards. I have been maintaining a table with my tabulated allele frequencies (without excluding any sample).

“This has led some popular writers to speculate that MAOA-2R might account for — or at least play a significant role in — the relatively higher rates of violent crime in African Americans. Not everyone agrees [21].”

If one writes, “Not everyone agrees,” it is good form to make sure that the source cited expresses some disagreement with what one wrote before “Not everyone agrees.”

“The rates of 2R are more than five times higher in African American males than in American white males, at least in the Add Health sample.”

Yeah, I guess 55 is more than 5. Damn that Wikipedia troll! Choe et al, which you cited, found it in 6% of black men and 0% of white men, so maybe it’s infinity times more common. Seriously, considering how rare it is in whites and Asians, why should we believe that those rare exceptions are actually genetically 100% white or Asian?

“Although genes affect individual differences in behavior, the effect of each individual gene is usually small.”

I think you meant to say “allele.” If the effects of individual genes are usually small, then missense mutations that completely shut off the gene and eliminate the protein should have little effect. Of course, you failed to mention the missense mutation specific to MAOA, which causes Brunner syndrome. The effect of Brunner syndrome on behavior is not small.

“The more common low-activity variant, 3R, interacts with adverse social effects such as childhood maltreatment. But other possible environmental factors, which conceivably could interact with the 2R, may not have been explored in-depth as yet.”

I think Fergusson et al did the most in-depth analysis of various environmental factors. Interestingly, the interaction effect of IQ on violence was more powerful than the interaction effect of childhood maltreatment. I’m afraid that you’ll have to look up for yourself whether African Americans differ from whites and Asians in average IQ because that is outside my area of expertise.

“Using PET imaging scans, these researchers found no correlation between MAOA brain levels and MAOA gene variants.”

However, Alia-Klein et al did find MAOA promoter effects on anger in an fMRI study. That study and Buckholtz et al found MAOA gene effects on the amygdala. Cerasa et al found that the gene influenced orbitofrontal cortical thickness with MRI. Buckholtz et al and Cerasa et al had much larger samples than the 34 men in Shumay et al. Shouldn’t you have mentioned those findings?

“Nonetheless, their results suggest that MAOA brain levels, which affect mood, are at least partially regulated by non-genetic factors — i.e., epigenetically.”

Of course, genes do influence epigenetics. In fact, the “environmental” interaction factors, like childhood maltreatment, might also have a component of heritability. Wong et al found that, compared to women, epigenetics of MAOA in men is minimal, low in variance, and high in hereditary influence. Pinsonneault et al was unable to detect any MAOA methylation in men. Philibert et al found less MAOA methylation in men and that MAOA methylation had no effect on antisocial personality disorder in men or women. That seems like a relevant finding.

“The jury is still out on whether 2R, the rare MAOA gene, acts independently of the environment (and independently of other genes) to shape antisocial personality traits.”

First of all, is MAOA-2R rare in Africans? A common definition of a rare allele is having an allele frequency less than 5%. It might not be rare in African-American men. We can extrapolate to the higher allele frequency in a population of Africans who are not racially mixed. All of the evidence we have on MAOA-2R, so far, suggests that it has a powerful effect independently of environment. The assumption is that this distinguishes MAOA-2R from MAOA-3R, which supposedly only has a gene-environment interaction effect. A recent meta-analysis of 31 studies actually disproved this and found that MAOA-3R has a slight effect on antisocial behavior independent of interaction factors.

Pigliucci allowed me to post this comment only so that others could harass me with baseless ad hominem, but he censored all of my other responses.

Exposing falsehoods about the warrior gene is nothing new for me, but this is different. It might be hard to believe that a respected scientist like Steven Pinker or an experienced writer like John Horgan would fall for the idiot test or that Scientific American, The Chronicle of Higher Education, and various journals and book publishers would reprint it. While one might not expect such incompetence from these sources, no evidence proves malfeasance. Also, Oubré’s mischaracterization of the science of MAOA epigenetics and brain imaging (also see Lei et al) is likely but not positively deceptive. In other words, she probably came across the evidence against her thesis and chose to keep it to herself, but one cannot absolutely demonstrate this as such. However, she unmistakingly lied when she attributed Wikipedia data to the Add Health subsample of the famous, widely used National Longitudinal Study of Adolescent Health database.

Interestingly, the idiot test almost constitutes a photographic negative of this fraud. The original copy-and-paste error by Rod Lea and Geoffrey Chambers first appeared in a scientific journal—perhaps not a highly respected journal, but a journal nonetheless—and subsequently spread to the public through mass media. This time, misinformation sprouted from the lowly, anonymously edited Wikipedia and traveled up the media food chain to scientific blogs. The Wikipedia page for MAOA originally contained correct information that I and other responsible agents copied correctly from peer-reviewed studies. Then, someone identified only by their Internet Protocol address, 76.78.226.57, began altering the data. One can observe from this person’s contributions page, that he or she has a history of altering numbers in Wikipedia that relate to immigration and ethnicity helter-skelter without providing new sources. On March 22nd, the offender made three unsourced edits to the same group of numbers on the MAOA page. At 2:25, the change was as follows:

Two minutes later, another change occurred:

At 23:55, the offender changed the same numbers, again:

This allowed for an error of an order of magnitude in Oubré’s numbers. So, who is 76.78.226.57? Is she Oubré? Is he Pigliucci? Who knows? Maybe he is Eric Holder. Nobody who knows is saying.

Massimo Pigliucci “Editor-in-Chief”

To prevent confusion among the lay public, I politely asked Scientia Salon editor-in-chief Pigliucci for an official correction in this e-mail:

You posted my corrections for "The Extreme Warrior gene: a reality check" as a comment. However, the errors were quite serious, such as claiming that data from Wikipedia (which was false information) actually came from the National Longitudinal Study of Adolescent Health. Such errors should not only be addressed by an outsider's comment. As the editor-in-chief of Scientia Salon, you should see that someone actually investigates my claims and posts a complete correction, if true. Alternatively, you could direct me to the appropriate authority within your site who handles corrections.

Pigliucci could not bother himself with more than a curt reply.

your comment has been published, so I’m not sure what additional action you expect from me, or why.

I tried repeatedly.

Yes or no, did Alondra Oubré falsely claim on your site that information she took from Wikipedia had actually come from the Add Health subsample of the National Longitudinal Study of Adolescent Health? If yes, was the information from Wikipedia all accurate? If she falsely attributed false information from Wikipedia, why do you refuse to post an official correction at the end of her piece, as any reputable source of information would? I noted numerous other errors, but this one in particular seems especially egregious because it reveals a lack of integrity and provides a conduit for anyone to make up information on Wikipedia and disseminate it through disreputable blogs.

No reply came.

As shown by her citations, Oubré obviously intended her perversion of MAOA science as a rebuttal to Wade. Less than three weeks prior, Pigliucci spent forty-two minutes in a podcast expatiating the standard semantic criticism that has amounted to basically the entirety of the fundamentalist anthropologist attack on Wade’s book. They call Wade a racist, and, in modern civilization, racists might be preferred to pedophiles but are considered far worse than necrophiliacs, cannibals, terrorists, zombies, Democrats, rapists, and even boy-band alumnae. Wade spent a good portion of his book criticizing white supremacy and called a book by JP Rushton racist in an interview. If idiotic anthropologists label every prestigious intellectual with whom they disagree a white supremacist, then the desire to be white supremacist among average white folks will grow like the tuition rates that young people pay to hear idiotic anthropologists bloviate. The colloquial definition of racism is the belief that average ability and tendency differences (stereotypes) exist between peoples grouped by place of origin. Heritability mathematics has nothing to do with it. Therefore, all anti-racists are racists. Actually, I would like to see the forces of good defeat white supremacy, which is why I know that the perceptual and strategic superiority lies with the recognition that the face of neo-Nazi white supremacy is the one covered in tattoos.










Alia-Klein N, Goldstein RZ, Tomasi D, Woicik PA, Moeller SJ, Williams B, Craig IW, Telang F, Biegon A, Wang GJ, Fowler JS, & Volkow ND (2009). Neural mechanisms of anger regulation as a function of genetic risk for violence. Emotion (Washington, D.C.), 9 (3), 385-96 PMID: 19485616

Balciuniene J, Syvänen AC, McLeod HL, Pettersson U, & Jazin EE (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), 157-63 PMID: 11231895

Buckholtz JW, Callicott JH, Kolachana B, Hariri AR, Goldberg TE, Genderson M, Egan MF, Mattay VS, Weinberger DR, & Meyer-Lindenberg A (2008). Genetic variation in MAOA modulates ventromedial prefrontal circuitry mediating individual differences in human personality. Molecular psychiatry, 13 (3), 313-24 PMID: 17519928

Cerasa A, Cherubini A, Quattrone A, Gioia MC, Magariello A, Muglia M, Manna I, Assogna F, Caltagirone C, & Spalletta G (2010). Morphological correlates of MAO A VNTR polymorphism: new evidence from cortical thickness measurement. Behavioural brain research, 211 (1), 118-24 PMID: 20303364

Ficks CA, & Waldman ID (2014). Candidate Genes for Aggression and Antisocial Behavior: A Meta-analysis of Association Studies of the 5HTTLPR and MAOA-uVNTR. Behavior genetics PMID: 24902785

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

Gilad Y, Rosenberg S, Przeworski M, Lancet D, & Skorecki K (2002). Evidence for positive selection and population structure at the human MAO-A gene. Proceedings of the National Academy of Sciences of the United States of America, 99 (2), 862-7 PMID: 11805333

Huang YY, Cate SP, Battistuzzi C, Oquendo MA, Brent D, & Mann JJ (2004). An association between a functional polymorphism in the monoamine oxidase a gene promoter, impulsive traits and early abuse experiences. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 29 (8), 1498-505 PMID: 15150530

Koen L, Kinnear C, Corfield V, Emsley R, Jordaan E, Keyter N, Moolman-Smook J, Stein D, & Niehaus D (2004). Violence in male patients with schizophrenia: risk markers in a South African population Australian and New Zealand Journal of Psychiatry, 38 (4), 254-259 DOI: 10.1111/j.1440-1614.2004.01338.x

Kunugi H, Ishida S, Kato T, Tatsumi M, Sakai T, Hattori M, Hirose T, & Nanko S (1999). A functional polymorphism in the promoter region of monoamine oxidase-A gene and mood disorders. Molecular psychiatry, 4 (4), 393-5 PMID: 10483059

Lei H, Zhang X, Di X, Rao H, Ming Q, Zhang J, Guo X, Jiang Y, Gao Y, Yi J, Zhu X, & Yao S (2014). A Functional Polymorphism of the MAOA Gene Modulates Spontaneous Brain Activity in Pons. BioMed research international, 2014 PMID: 24971323

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

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

Pinsonneault JK, Papp AC, & Sadée W (2006). Allelic mRNA expression of X-linked monoamine oxidase a (MAOA) in human brain: dissection of epigenetic and genetic factors. Human molecular genetics, 15 (17), 2636-49 PMID: 16893905

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

Sabol S, Hu S, & Hamer D (2014). A functional polymorphism in the monoamine oxidase A gene promoter Human Genetics, 103 (3), 273-279 DOI: 10.1007/s004390050816

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

Williams RB, Marchuk DA, Gadde KM, Barefoot JC, Grichnik K, Helms MJ, Kuhn CM, Lewis JG, Schanberg SM, Stafford-Smith M, Suarez EC, Clary GL, Svenson IK, & Siegler IC (2003). Serotonin-related gene polymorphisms and central nervous system serotonin function. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 28 (3), 533-41 PMID: 12629534

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

Young SE, Smolen A, Hewitt JK, Haberstick BC, Stallings MC, Corley RP, & Crowley TJ (2006). Interaction between MAO-A genotype and maltreatment in the risk for conduct disorder: failure to confirm in adolescent patients. The American journal of psychiatry, 163 (6), 1019-25 PMID: 16741202

Yu YW, Tsai SJ, Hong CJ, Chen TJ, Chen MC, & Yang CW (2005). Association study of a monoamine oxidase a gene promoter polymorphism with major depressive disorder and antidepressant response. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 30 (9), 1719-23 PMID: 15956990

Christopher Irwin Smith is an Idiot

Poopy-Faced Idiot
Deep inside an underground compound within the evil lair of the American Anthropological Association, Lord Skeletor summoned a scientist to spread falsehoods about the science of monoamine oxidase A, the warrior gene. That scientist was Christopher Irwin Smith, Associate Professor of Biology at Willamette University. Dr. Smith set about penning a diatribe full of errors and misleading innuendo. “I shall post this on the Internet and not allow better-informed people to comment on it,” he muttered before mustering an evil cackle that echoed through his dark private chamber.

Our investigators have uncovered the following especially telling response comment:

Dr. Smith,

Your impressive background prevents me from having any sympathy for you regarding the multiple egregious errors in this post. Probably the worst aspect of it is the timing because the last two years have produced two important meta-analyses confirming MAOA as an aggression and antisocial behavior gene. I’m guessing you have no awareness of either one.

“…Nielsen and Williamson’s studies were able to identify many regions in the genome that appear to have experienced recent natural selection, but MAO-A is not one of them.”

You neglected to mention that their study examined single-nucleotide polymorphisms, not repeat polymorphisms, like either of the functional MAOA-uVNTR promoters. The same is true for Voight et al.

“it is likely that these genetic variants are not –on their own– associated with violent or impulsive behavior… Simply carrying the ‘low expression’ allele in the MAO-A promoter does not have any effect at all on impulsivity or aggression.”

I doubt that you would have written this if you had been aware of the new meta-analysis by Ficks and Waldman, which came to the opposite conclusion.

“Instead, genetic variation in the MAO-A promoter seems to make some children less able to recover from abuse and childhood trauma, and therefore more likely to act out later in life (Caspi et al. 2002; Widom & Brzustowicz 2006).”

You are misrepresenting the findings of Caspi et al. It is MAOA-4R, not MAOA-3R that has the effect, which is a protective effect. According to Caspi et al, abuse could not affect those with MAOA-4R at all. Other studies have found the same protective effect against high testosterone levels and low IQ. Byrd and Manuck recently provided a meta-analysis verifying the abuse-MAOA interaction effect.

“Indeed, genetic variants associated with lower resilience to trauma are most common in Asian populations, not African ones (Sabol et al. 1998).”

Are you seriously saying that 61.0% is significantly higher than 59.1%? I think you must have been thinking about the copy-and-paste error by Lea and Chambers that claimed that 77% of Chinese men have MAOA-3R. I have labeled that the “idiot test” because it has caught many highly credentialed idiots who were trying to do the same thing that you are trying to do now: brush off decades of good research on MAOA. Ficks and Waldman only found a modest main effect of MAOA-3R, so you would need to argue not only that the gene is as common in Asians but also that the interacting factors (child abuse, high testosterone, an IQ less than 85) are as common in Asians, as well. Then, there is the issue of MAOA-2R….

“Note that Sabol study did not consider differences between populations in the frequencies of the ‘2-repeat’ alleles that Wade references…”

Did not consider? Gee, that is an interesting way of putting it. Of course, they tried to determine the allele frequency of each kind of allele in that VNTR, and they reported absolutely no instances of MAOA-2R in any group out of a total sample of over 2,000 X-chromosomes. MAOA-2R had not been discovered until the next year by Kunugi et al. Ever since, we have known that MAOA-2R is rare in whites but not that rare. Something is seriously wrong with the Sabol et al allele frequencies.

“To my knowledge, the frequency of the 2-repeat allele across populations has not been extensively measured; studies that have looked at its incidence appear to have focused on specific cohorts in the US as part of epidemiological studies.”

Is this your way of trying to cast doubt upon the allele frequencies reported in the literature for MAOA-2R in African-American men? Establishing an allele frequency does not require a 31-study meta-analysis. We have consistent findings from multiple studies that MAOA-2R is many times more common in African-American men than either white or Asian men. Would you like to read each study?

The Warrior Gene, Back from the Grave

Recently I read a phenomenal book called A Troublesome Inheritance by Nicholas Wade. It has science and sociological “speculation,” but most of the speculation actually just cited the speculation of other writers. I would say the scholarship was relatively good compared to other works of popular science. I assumed that critical appraisal would universally approve, but I would like to report that this was not entirely true. The book was actually panned by a group of people called “anthropologists,” who are almost like real scientists with their own journals and everything. Anthropologists only had one criticism: they wished Wade had scratched every use of the word “race” and written in “population,” which is ironic because a recent survey of anthropologists determined that “racist” was their second most commonly used word after “the.” It is troubling that while anthropologists have taken their courageous stand against racism, they are as of yet blind to the scourge of populationism. I think it was Confucius who said, “We have come so far but have so much farther to go.” I think “further” would have been more grammatically correct, but distance is a metaphor, and “farther” resembles a parallel construction.

Nicholas Wade took up my cause of drawing attention to an allele of monoamine oxidase A, "the warrior gene," that is rare in non-Africans and thought to predispose one to violence. However, an anthropologist named Jennifer Raff succeeded in invading the field of genetics, and she countered our claim by posting a study by Vassos et al.

"MAO-A’s effects (as well as those of any other candidate gene known at this point) appear to be very, very minor (if they even exist at all)…"

Good gravy! You mean to tell me that all that research that I have been following all these years has been debunked by a single study?! Well, I decided that before I take the drastic step of erasing half of my blog, I should actually read the study. Then, I read the other study that was on basically the same subject and published at almost the same time but that came to the opposite conclusion. Then, I magnanimously offered up my very own blog as a moderated forum for a discussion with the correspondence authors of each study. They did not respond to my request, so I shall do what I usually do and post the empty-chair interview questions.

Questions posed to Dr. Evangelos Vassos:

1. Your study mentions “increased aggressive behavior in … MAOA knockout mice.” Why does your study make no mention of the equivalent MAOA knockout condition, Brunner syndrome, in humans?
2. Your study concludes that “it is unlikely that few candidate genes explain a complex behavior like aggression” and “aggression and even violence are complex behaviors.” Does the existence of Brunner syndrome contradict your conclusions?
3. For MAOA in females, your study included Guo et al, “The VNTR 2 repeat in MAOA and delinquent behavior in adolescence and young adulthood: associations and MAOA promoter activity.” Unlike other studies on MAOA, that study obviously defined MAOA-2R as a distinct allele rather than another “low-activity allele” paired with MAOA-3R. How did your study account for this difference? Why did your study not note that Guo et al found a main effect of MAOA-2R, for which no attempt at replication with a different sample has been attempted?
4. Have you heard of the meta-analysis by Ficks and Waldman, “Candidate genes for aggression and antisocial behavior: A meta-analysis of association studies of the 5HTTLPR and MAOA-uVNTR”? Would you care to comment on how that study’s meta-analysis for MAOA differs from your meta-analysis?
5. Unlike Ficks and Waldman, your meta-analysis elected to include studies that used clinical psychiatric patients with mental illnesses and substance abuse problems. In fact, I count that 12 of the 17 studies on MAOA in males used such clinical patients. What is your rationale for this approach?
6. Supplementary Table 1 shows sample sizes for Gerra et al and Koller et al that suggest that your study did not consider the effects of MAOA on the aggression or hostility of each study’s control sample. It appears that you excluded the control samples and only considered the effects on the alcoholic or heroin-dependent subjects. Why is that?
7. Your meta-analysis found studies partly by scanning “reference lists of all included studies,” but these reference lists included multiple studies that Ficks and Waldman included but not your meta-analysis, specifically Manuck et al, Jacob et al, Beitchman et al, and Kim-Cohen et al. Manuck et al was listed in 4 of the 17 studies for MAOA in males. Ficks and Waldman were able to include 31 MAOA studies despite excluding studies of other psychiatric disorders, and neither meta-analysis included Williams et al (2003), Rosenberg et al (2006), Nilsson et al (2007), or Kuepper et al (2013). Why were these studies not included?
8. Like other negative studies of MAOA, your meta-analysis criticizes the entire project of candidate-gene behavioral genetics, saying “Our study provides evidence that the candidate gene approach has not succeeded in identifying genes associated with these outcomes. This is consistent with recent observations in the field that candidate gene studies of human characteristics and complex diseases at large have failed to produce consistent and clinically useful findings.” Ficks and Waldman included more studies for MAOA and found a modest positive effect, consistent with other lines of evidence (MAOA knockout mice, Brunner syndrome, gene-environment interaction, brain imaging, etc.). Should their meta-analysis have made just as strong of a judgment in favor of the usefulness of a candidate-gene approach to studying behavioral genetics? Why do only negative studies reflect upon this issue?
9. Would you be willing to have your responses appear unedited on my personal blog, The Unsilenced Science?

Questions posed to Courtney Ficks:

1. For MAOA, your study included Guo et al, “The VNTR 2 repeat in MAOA and delinquent behavior in adolescence and young adulthood: associations and MAOA promoter activity.” Unlike other studies on MAOA, that study obviously defined MAOA-2R as a distinct allele rather than another “low-activity allele” paired with MAOA-3R. How did your study account for this difference? Why did your study not note that Guo et al found a main effect of MAOA-2R, for which no attempt at replication with a different sample has been attempted?
2. Have you heard of the meta-analysis by Vassos, Collier, and Fazel, “Systematic meta-analyses and field synopsis of genetic association studies of violence and aggression”? Would you care to comment on how that study’s meta-analysis for MAOA differs from your meta-analysis?
3. It appears that their study was published by a journal with a higher impact factor than yours (15 versus 3 in 2012), but they elected to include studies that used clinical psychiatric patients with mental illnesses and substance abuse problems and included fewer studies on MAOA. Why is your study in a journal with a lower impact factor? Is it possible that the outcome of their study was ideologically favored over that of your study?
4. Did you consider including the studies by Williams et al (2003), Rosenberg et al (2006), Nilsson et al (2007), or Kuepper et al (2013)? If so, why were these studies not included?
5. Like other negative studies of MAOA, Vassos et al criticized the entire project of candidate-gene behavioral genetics, saying “Our study provides evidence that the candidate gene approach has not succeeded in identifying genes associated with these outcomes. This is consistent with recent observations in the field that candidate gene studies of human characteristics and complex diseases at large have failed to produce consistent and clinically useful findings.” Your study found a modest positive effect, consistent with other lines of evidence (MAOA knockout mice, Brunner syndrome, gene-environment interaction, brain imaging, etc.). Why didn’t your study conclude with just as strong of a judgment in favor of the usefulness of a candidate-gene approach to studying behavioral genetics? Why do only negative studies reflect upon this issue?
6. Your study claimed that “there is growing evidence that we must be wary of” gene-environment interaction findings. However, Byrd and Manuck published a meta-analysis last year that seemed to show a robust gene-environment interaction for MAOA and childhood maltreatment. Some GxE interaction studies for MAOA have had positive results for fairly common environmental factors, like an IQ less than 85, high cerebral spinal fluid free testosterone, and poverty. Is it possible that the totality of suspected environmental factors are so common that your finding of a modest main effect was actually picking up these effects, even though you didn’t try to isolate them? Should those factors be control variables in this type of research?
7. Would you be willing to have your responses appear unedited on my personal blog, The Unsilenced Science?

I completely empathize with the decisions of Ficks and Vassos to ignore the interview requests. Ficks probably did not want to answer a question that would insult a prestigious journal, like Molecular Psychiatry. Dr. Vassos probably didn’t feel like answering because he must know that his study is complete garbage, and he doesn’t want to talk about it.










Ficks CA, & Waldman ID (2014). Candidate Genes for Aggression and Antisocial Behavior: A Meta-analysis of Association Studies of the 5HTTLPR and MAOA-uVNTR. Behavior genetics PMID: 24902785

Vassos E, Collier DA, & Fazel S (2014). Systematic meta-analyses and field synopsis of genetic association studies of violence and aggression. Molecular psychiatry, 19 (4), 471-7 PMID: 23546171

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

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.










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