Half Sigma’s flawed post on DTNBP1

Half Sigma’s flawed post on DTNBP1

A while back, Mark and I were working on a comprehensive post which would try to tally the results of the various IQ-gene studies to see what they said about racial differences. We began this quest bright-eyed and hopeful that we would help contribute to ending a calamitous debate that has gone on for way too long. However, as we learned more about genetics, and these studies in particular, we came to realize that it’s too early to take IQ-genes seriously.

We began with an approach similar to what Half Sigma did 2 years ago with the DTNBP1 gene. However, we soon learned that this approach was incredibly flawed and misleading. I wasn’t going to write this post, but recently Half Sigma’s DTBP1 post was linked from Reddit and tens of thousands of people are viewing it. When I saw that, I frustratedly criticized HS. He responded that I should give a more diplomatic and reasoned response, so here it is:

  1. You cannot simply add up SNPs from the same gene or chromosome. Half Sigma simply adds the observed effects of the SNPs to one another, ignoring that the alleles are highly correlated with one another, and not independently inherited, which is referred to as linkage disequilibrium (LD). The study that Half Sigma used provides the following table of LD for its SNPs:

    rs2619539rs3213207rs1011313rs2619528rs760761rs2619522rs2619538
    rs26195390.1560.1110.00.00.0010.055
    rs32132071.00.0140.3340.4030.340.076
    rs10113130.9161.00.0370.0330.0360.081
    rs26195280.0240.9551.00.8380.7370.128
    rs7607610.01511.00.960.8540.166
    rs26195220.040.9551.00.8670.960.182
    rs26195380.2420.8230.8250.6480.7720.778

    As can be seen in this table, pairwise LD goes as high as 1.0, meaning that two of the alleles are always inherited together. Adding these SNP’s together is therefore like counting them twice.

  2. Group comparisons require replication in both groups. Because different populations have systematic genetic and environmental differences, an effect in one group may not occur in another. The study that Half Sigma uses relies primarily on a (small) sample of Dutch people. It is unclear whether these effects would exist in a population of African ancestry, let alone another European one.
  3. Candidate-gene association studies are not reliable. This is the most important point. Candidate gene association studies have largely failed to replicate. In fact, there have been no common IQ polymorphisms which have been replicated. Genome-wide association studies, which don’t suffer as severely the various biases of candidate-gene association studies like publication bias or the winner’s curse have not shown common SNP-associations with IQ.

    IQ is highly heritable, so the problem is the current methods, not the search for genes. With the development of sequencing technology and huge cohorts, we will be able to see the genes that are really behind normal IQ variation. With replication in multiple ethnicities and races, we will also see to what extent various genes and environments are responsible for group differences. There’s no need to make proclamations of victory for hereditarianism or environmentalism in the mean time.

Razib Khan