“While most blank slaters continue to ignore it and the retro-racists use bits as they see fit, some of us are ploughing through it to learn something new. … However, I am not convinced that we are particularly close to obtaining that sort of information.” On these genetics blogs I am constantly hearing this mealy-mouthed blather about how complex human genetics is and that no individual genes are important. You sound like agnostics lecturing atheists. I can just imagine you lecturing doctors for prescribing drugs that target neurotransmitters. If a gene cannot have an important effect on a behavior, then why should a single type of molecule have an important effect on a behavior? You are all pointing to these pointless GWAS that focus entirely on SNPs, neglecting gene expression despite the ironic title of the blog. When a study attacked the depression gene, your blog attacked candidate gene research. When that study was disproved, your blog was silent. Candidate gene research gives us a small amount of immediately useful information. GWAS research gives us hope that someday, hopefully, we shall know a lot more about a more significant genetic contribution to behavior. Great, but that is not low-hanging fruit. This wouldn’t bother me if there was some attention being paid in the serious genetics blogosphere to candidate gene research. Blogs like Gene Expression used to do that. Now you have become Apostles for Ignorance.

Dick et al and Viding et al also found no significant SNPs for conduct disorder and antisocial personality disorder. However, this is hardly the totality of common genetic variation. Most of the candidate gene research is focusing on promoter tandem repeats in dopamine- and serotonin- affecting genes. For instance, 5-HTTLPR was just redeemed as an important factor in depression predisposition after a new meta-analysis discredited a biased 2009 paper. It is a not a gene at all, but rather a promoter for SLC6A4.

I am intrigued by the MZA versus MZT study, but Raven?s Progressive Matrices tests have been more vulnerable to the Flynn effect than other IQ tests. You are saying that vulnerability to the Flynn effect is associated with g-loading, but what if part of the Flynn effect is due to increased familiarity, which would reduce test accuracy at measuring intelligence? Comparing MZ twins to DZ twins may underestimate the genetic influence on IQ because 75% of MZ twins share the placenta, which Jacobs et al determined affects cognitive scores.

5-HTTLPR is the gene that Risch et al recently targeted in a meta-analysis on the gene-environment association with depression. They also glibly attacked MAOA research. Here are color-coded research summary tables of the effects of the 3R and 4R alleles of MAOA on aggression. (Click to enlarge.) A few studies also link 5-HTTLPR to a modest effect on aggression.

I mistakenly wrote that 98% of the non-whites were white or black. Please note that it should read "98% of the subjects were white or black." 
 
Here is the link to Catherine Elton's essay.

Chi, 
 
The Gary Hook "essay" is hilarious. How ironic that those who believe that race is a social construct want us to believe that this gene acts differently in "non-whites." In fact, Widom and Brzustowicz suggested that biological racial differences could explain their finding of no protective effect from the 4-repeat MAOA VNTR allele in non-whites. They wrote, "given the differences in the allele frequencies in the white and non-white populations for the MAOA VNTR promoter polymorphism (observed in this study), as well as other polymorphisms within the MAOA gene and throughout the genome, it could be that there are substantially different frequencies of other MAOA modulating polymorphisms in white and non-white populations." Hook did not pass along that idea, preferring to only mention possible "environmental stressors." He criticizes applying what we know about the MAOA gene to Maori, yet he thinks that what Widom and Brzustowicz determined about "non-whites" can be generalized to include Maori. 
 
Let us be clear. Widom and Brzustowicz did not prove that MAOA acts differently in non-whites. They only included 98 non-white males in their study. In contrast, Huang et al included 110 blacks, 10 Asians, 79 Hispanics, and 8 "other." Huang et al found that MAOA influences impulsivity. Beaver et al included 383 blacks and 1484 whites, and they found that MAOA influenced violent behavior. Weder et al included just 58 black and biracial subjects, but they found that the MAOA-environment interaction effect on aggression was significant specifically in that group. Of course, all these studies have somewhat low power, but the point is that Widom and Brzustowicz did not prove MAOA acts differently in non-whites. Even within their tiny 98-subject group of non-whites, they claimed that a sub-group of blacks also lacked a significant gene-environment interaction effect. They did not bother to offer numbers for how many of these mere 98 non-white males were black, even though a significant portion of the subjects were from a previous study in which 98% of the non-whites were white or black. They were hiding this information because their data suggest that blacks, compared to whites, have an order of magnitude more of the 2-repeat MAOA VNTR, which is far more likely to predispose to violence than the 3-repeat allele that earned MAOA the "violence gene" label. 
 
For his part, Hook does not seem to understand the difference between the 3-repeat allele and Brunner syndrome, which completely shuts off MAOA. He thinks Brunner syndrome could not offer Darwinian advantage. Therefore, a more modest level of aggression from the 3-repeat allele would not, either. This was a poorly written attempt to browbeat scientists, much like the recent Catherine Elton essay in Time.  
 
The Ahn et al study on hormones is relevant to MAOA because hormones influence MAOA expression. I am working o
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less than 0.06%). 
 
? 
 
In a study of prostate cancer, laser capture microdissection (LCM) was used to dissect prostate tumors into cancerous and noncancerous tissue. Initial results [Alvarado et al., 2005] supported the traditional hypothesis of somatic mutations as the causal agents for carcinogenesis, because genetic alterations in the androgen receptor gene (AR) were found in cancerous tissues, but not in blood. However, in a follow-up study, AR alterations were detected in completely disease-free prostate tissues, remarkably even in prostate tissue from a 1-year-old child [Sircar et al., 2007]. Thus, unlike blood and other tissues, prostate tissue whether diseased or nondiseased and of varying age and maturity, contained variants of the AR gene. 
 
? 
 
The presence of SNPs in nondiseased AA tissue suggests that they may be present prior to appearance of disease and may be a consequence of vascular development and maturation. Their presence might be at least partially responsible for the increased susceptibility of AA tissue to aneurysm formation. A possible alternative explanation of their genetic origin is that within nondiseased AA tissues some BAK1 SNP-containing alleles can exist perhaps as ??minority?? forms, in a similar manner to what we have observed in prostate tissue [Sircar et al., 2007]. That is, they are only initially present in a very few cells within normal aortic tissue and are then selected for when tissue and cellular conditions change. 
 
From this I gather that these are genuine differences in genotype between tissue and blood samples. Therefore, GWAS?s could be inaccurate because they assume that blood samples, which I believe is referring to leukocytes, contain DNA equivalent to the target tissue.

(continued)

Do you know if the mutation in question was found in the majority of aortic or aortic aneurism cells? 
 
I shall quote the relevant sections: 
 
To establish a reference sequence we examined BAK1 sequence data from a number of databases (up to five) from different Caucasian populations as listed in the NCBI database (Table 1). 
 
? 
 
We collected tissue samples from a total of 31 AAA patients obtained at the time of surgical repair, together with matching blood samples, as well as five samples of normal nondiseased abdominal aortic tissue, that was obtained from a tissue bank. However, when BAK1 cDNAs from actual AAA tissue were sequenced gene alterations were found in three of the amino acids (a.a.) (Table 2), which were exactly the same as the rare SNPs that had been identified in the reference databases (Table 1). In two cases, coding region SNPs resulted in a change in a.a. 42 from arginine to histidine (dbSNP# rs1051911:G>A), and in a.a. 52 from valine to alanine (dbSNP# rs1051912:T>C) respectively (Table 2). In the third case a coding region SNP in a.a. 81 resulted in no change to the amino acid incorporated (dbSNP# 1051913:C>T). This initially suggested that these SNPs could be considered as possible factors in the formation of aneurysms. To confirm these observations, we sequenced BAK1 cDNAs from nondiseased abdominal aortic tissue. Our results somewhat surprisingly showed that the nondiseased tissue contained the same SNPs as the diseased tissue (Table 2). However, when matching blood from the patients was sequenced it was discovered that none of their BAK1 alleles contained any of the reported rare SNPs (Table 2). Thus, the results showed that aortic tissue, whether diseased or not, contained a number of distinct SNPs, that were not present in matching blood samples or in the vast majority (on average >99.4%) of reference sequence DNA (Table 2). However, of interest was that these SNPs had been observed in a very distinct minority of reference sequences (on average

Since you bring up the topic of IQ and genetics, I would like to end gnxp's deafening silence on the latest news about genome-wide association studies. Since these studies have found no "unequivocally associated" locus for IQ, it seems that a great multiplicity of genes affecting IQ could undermine a significant role for natural selection. Now a study of aortic aneurysms shows that blood samples failed to represent the somatic mutations of diseased and non-diseased tissues. Would this not undermine previous conclusions based on GWAS's, which rely on blood samples? I also wonder if the presence or absence of such somatic mutations could have functionality.

If one agrees that replication is the solution, then one typically turns to meta-analyses to resolve conflicting studies. Rather than disprove an association, studies with non-significant results will combine in the meta-analysis to narrow the confidence interval. Thus, they may actually support the association. This is illustrated by the Kim-Cohen meta-analysis for the gene interaction involving MAOA. This study included the largest of the three studies that unequivocally found non-significant results out of 13 or so addressing the 3-repeat and 4-repeat alleles in white males. 
 
Another important point for studies of gene and environment interactions is that a narrow definition of the environmental exposure can create a bias towards the null hypothesis. After all, the subjective assessment that really counts is that of each subject because their subjective experience determines their internal milieu. That is why I would tend to place greater faith in the Sjoberg et al study, despite a relatively small sample size, because it traded the environmental exposure for an objective measurement of testosterone and found a significant interaction effect with MAOA. 
 
I am also concerned about political bias determining what research is funded and by how much. I suspect this would affect sample size. Recall the plight of the Human Genome Diversity Project. I have sensed something similar, as I researched the MAOA gene. For example, Widom identified her subjects? racial background in 1989. She added them to her 2002 study on MAOA, but did not identify any of the subjects by race this time other than to call them white or ?non-white.? Likewise, Ellis and Nyborg felt they needed to defend their study of racial differences in testosterone levels, even as they advised scientists to be ?on guard against even the hint of any misuse of research findings.? Are these studies responding to political pressure?

The original 2002 Caspi et al study of MAOA did not consider the 2-repeat allele. Considering Brunner syndrome?s low MAOA expression and the consistent finding of a more extreme effect of the 2-repeat allele compared to the 3-repeat VNTR, Brunner syndrome should be seen as on a continuum with the 2-, 3-, and 4-repeat alleles. 
 
For those readers unfamiliar with this research, may I recommend my crash-course video: 
 
http://tinyurl.com/nj4spp

Wow. So you don?t believe that MAOA is a violence gene? So I guess you don?t believe in Brunner syndrome, either. WTF!

Sorry, GNXP. Another politically correct, pretentious attack on genetics research bites the dust. 
 
http://www.sciencedaily.com/releases/2011/01/110103161105.htm 
http://www.citeulike.org/user/achinerarias/article/8502880 
http://www.gnxp.com/blog/2009/06/another-candidate-gene-association.php

I thought I would draw your attention via Steve Sailer to a new paper defending race and a low-intensity debate on today’s Talk of the Nation about race. 
 
http://isteve.blogspot.com/2010/01/vindication-of-concept-of-race.html 
http://www.npr.org/templates/story/story.php?storyId=122620064 
 
Self-described race “agnostic” Dr. Esteban Burchard debated Pilar Ossorio and Alan Goodman (whom Sesardic quotes in the paper). 
 
Also, I mentioned in my new blog and video a new study about testosterone spikes in people with fewer CAG repeats (like African Americans), which, along with increased receptor transactivation, addresses the paradox of why black people do not seem to have significantly higher serum testosterone levels despite seeming to many to be more masculine than most whites and Asians. 
 
http://theunsilencedscience.blogspot.com/2010/01/epistemology-endocrinology.html 
http://www.youtube.com/watch?v=crYbmmQmaC4

New fossils shake up role of Africa in humanoid evolution: here, here, and here.