Monday, December 23, 2013

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


nooffensebut said...

sarcastic_f said:
“'Unsilenced Science' brags that 2-Repeat Allele of MAO gene increases shooting/stabbing in black men (with tiny n=5)”

5? It’s funny how the GWAS Jihadists (including Harvard scientists) are so bad with numbers. (See the “idiot test.”) GWAS Jihadists shouldn’t be forced to take biology or chemistry classes, since all they need to know is how to obtain very large sample sizes. The ideal study from their perspective would never exclude any subject for any reason. The largest number of cases (yes, cases, which is different from sample size) for MAOA-2R is eleven, which is eleven more than any GWAS has ever been able to study for this allele. However, it is worth considering whether the meta-analysis verification of MAOA-3R has bearing on the understudied MAOA-2R allele. Is it a completely different “gene” or a different “dose”? GWAS Jihadists want us to think it’s completely different, I guess, but SNPs can serve as “markers” for such things. Hmm.

I remember the good-old days when the geneticists wanted to show how smart they were by questioning the definition of “junk DNA.” Now, the MAOA-2R is as good as junk because no one has bothered to study it, yet, with a large sample. How much of this philosophy is based on a desire to avoid buyers’ remorse over a 23andMe purchase?

John Fuerst said...

Here's a modest proposal:

(First, read the following papers:
"Factor Analysis of Population Allele Frequencies as a Simple, Novel Method of Detecting Signals of Recent Polygenic Selection: The Example of Educational Attainment and IQ" & Correlation of the COMT Val158Met polymorphism with latitude and a hunter-gather lifestyle suggests culture–gene coevolution and selective pressure on cognition genes due to climate)

If you want, we could see if MAO-A allele variation correlates with international crime variation (and historic hunter gather lifestyle, etc.). We could then publish the results -- or give them to someone who would. This would advance the research at least a little. The logic is: if there was polygenic selection for domestication and if MAO-A is related to domestication, then we might expect to find a correlation between criminal rates and MAO-A on the international level. We can use Interpol stats: (If we found a significant positive correlation, the Pinkeresque critique -- i.e., East Asians have ... -- would be finished.) If you are interested, shoot me an email at or drop a comment at Human Varieties. I would do it myself but I haven't been following this issue.

John Fuerst said...

For allele frequencies, see for example, here:

Unfortunately, I'm not familial with the MAOA research.

nooffensebut said...

Thank you. I’m reading the studies, and they’re very interesting. I considered doing something like the educational attainment study, and I did do racial allele counting for obesity. I think effect sizes should probably also be used, in addition to allele frequencies. The COMT study seems to be arguing that COMT is an allele of large effect, even though it is a SNP, and GWAS have not found a SNP of large effect. There are many more reasons to believe that intelligence is a complex phenotype than there are reasons to believe that impulsive violence is so complex. In the case of MAOA, the gene, itself, is highly complex. The most studied versions are MAOA-3R and MAOA-4R. MAOA-3R has a verified behavioral phenotype when it interacts with child abuse, low intelligence, high testosterone, etc. It is most common in Africans and Asians. I am trying to campaign for more research on MAOA-2R, which appears to have a main effect and is most common in Africans. If all relevant factors are considered, the factors probably would fit rates of violent crime to some extent, but I think that is too obvious to warrant a dedicated study by me at this time. I do have a couple other projects on which I’m working at the moment. I am already working on compiling allele frequencies for the VNTR on all groups from all, or nearly all studies. You pointed me to allele frequencies on MAOA SNPs, which do not appear to have behavioral phenotypes, at least not for antisocial behavior. Studies that use SNPs as markers for MAOA tend to be false negatives. It is unfortunate that 23andme considers one of the SNPs to be the “warrior gene.”

Anonymous said...

Tachykinins and aggression.

Tachykinins are involved in activating "fast-twitch" muscles.

Notice how careful the authors are to avoid the third rail.

The finding that these neurons are present in the brains of male but not female flies indicates that this sex difference in aggressive behavior is genetically based. At the same time, Asahina stresses, finding a gene that influences aggression does not mean that aggression is controlled only by genes and always genetically programmed.
"This is a very important distinction, because when people hear about a gene implicated in behavior, they automatically think it means that the behavior is genetically determined. But that is not necessarily the case," he says.

Ask Not for Whom the Bell Curve Tolls said...

As though your despicable racist pseudo-science isn't enough, you add HUMOUR. There should be a law. Hopefully there soon will be.

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.

Or name it after the greatest political movement of your lifetime: Neo-con syndrome. But perhaps that should be reversed for one of the many interesting features in the genomes of Wolfowitz, Perle et al.

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.

Or Vibrancy Syndrome. Cultural-Enrichment Syndrome. Diversity-Is-Our-Strength Syndrome.

Anonymous said...

i would like to know what you think of this article differentiating castes.

It seems indian americans on wikipedia are the wealthiest american diaspora. Per household income and academic success is second to non...

What do you think will happen over the next 50 years in terms of embro selection as well as gene therapy. There is by the way a company now in China looking for high IQ genes funded in part by the government. BGI shenzhen. Stephen Hsu has a n and a half hour lecture called the genetic architecture of intelligence which I loved and I think you would to. He even said that you could push intelligence 30SD above average with no negatove fitness consequences at abou 1:16:00. I recommend a watch. Forgive any spelling informalities.

nooffensebut said...

I have met many talented second-generation Indian-Americans. I think their success calls into question simplistic notions of ethnic regression to the mean, and I think many of them have somewhat dark skin and probably wouldn’t be Brahmin. Indian-American achievements and IQ obviously benefit from H1B selectivity, which is related to their English-language inheritance. My work with SAT data matches other evidence of rapidly rising capabilities of Asians, so the date of the IQ study is relevant. I think the example of Indian-American success calls for the more moderate, circumspect approach that I have taken by focusing on large-sample high-stakes exams and plotting on a timescale.

I have written two posts that address the work of Steve Hsu and BGI, which I am following closely.

Anonymous said...

This paper was just published in the flagship criminology journal. Ha! -- it completely tears down everything you have ever said about genes and crime. Your blog should be abolished now that there is solid evidence disclaiming what you talk about on this blog and the research that you choose to cite. Genes do NOT matter for crime. I expect an apology on your blog for writing what you wrote. Ha!

nooffensebut said...

Well, I'm convinced! :) Decades of research are completely torn down by one "critique of heritability study methods," presumably including both quantitative genetics methods and the corroborating Yang-Visscher heritability estimates.


Meanwhile, a new study finds a main effect of MAOA-3R on African-American males for externalizing problems at age 5 and an interaction with mother's discipline on juvenile court petitions. Six percent of African-American males have MAOA-2R, but none of the whites have it. African-American men are infinity times more likely to have MAOA-2R than whites!!!

nooffensebut said...

Here's a video of the authors of your study saying that African Americans experience discrimination, which causes them to commit crime, but white people never experience discrimination. I assume that whites must experience more racial discrimination than Asian Americans because whites commit more crime than them.

Anonymous said...

Keep telling yourself that. They show that ALL heritability studies are wrong so you simply can't go back and discuss those or say that there are lots of studies showing genes have impact. You are backed into a corner and you need to stop saying these things. I know that the entire sociology and criminology fields will be convinced by this powerful study, why can't you be! These are PhDs and academics! Ha! Burt & Simons to the rescue!

nooffensebut said...

Your study proves GWAS heritability estimates wrong, just like Big Tobacco proved nicotine isn't addictive, 1998 proved global warming is a hoax, Robert Atkins proved not eating your vegetables is good for your heart, Stephen Jay Gould and Malcolm Gladwell proved IQ doesn't matter, Ray Comfort's banana proved creationism, and Jenny McCarthy proved vaccines cause autism.

Anonymous said...

Nothing but rhetoric and red herrings in your comments about the paper. It's not my paper, but it soon will be THE landmark study of the year that tears down your blog and all of the "research" that it uses.

nooffensebut said...

Criticism of twins studies is not new. GWAS are not twins studies.

Anonymous said...


Holy shit, thanks for the laugh. That sociology video was literally comedy.