Common traits and GWA

2 minute read

Worth reading: Daniel MacArthur comments on 23andMe’s reporting of genome-wide associations coming from their customer surveys of traits. The skinny:

23andMe has also nailed down a handful of genuinely novel genetic associations: a massively significant association between an olfactory receptor region and "asparagus anosmia" (the inability to smell asparagus in one's own urine), and two regions associated with hair curl.

On the topic of how genomics will go in the future, I think this section of MacArthur’s post is revealing:

23andMe faces an unusual challenge that standard academic GWAS consortia don't: the possibility that a subject will give a biased trait report after seeing their own genetic data. This was powerfully illustrated by results from the "athlete gene" ACTN3 (a gene close to my own heart). There was no association between the athletic performance-associated variant in this gene and self-reported sprinter/endurance preference in individuals who hadn't seen their genetic data - but in individuals who had already seen their genotype there was a marked shift towards carriers of the "sprint" or "endurance" allele self-identifying with those respective categories. In other words, people were altering their self-reported athletic affiliation on the basis of their genotype; Eriksson estimated that around 25% of individuals must be shifting their self-identification to explain the effect, a staggeringly large number.

This is such a common cognitive bias that it shouldn’t surprise anyone, but it sure wrecks the statistics. Once people “know the right answer”, they start aiming for it. That’s why placebo-controlled blind trials are so necessary for medical treatments, it’s also why so much genetic work applied to anthropological questions is bunk (because the mere knowledge of which dates are important, combined with many free parameters, will always allow one to generate the “right” answer).

Suppose I genotyped a bunch of people for OCA2/HERC2-linked SNPs and compared with eye color. There’d be a lot of people who, knowing the “right” answer, would push their eye color. You know, “I mean, maybe they’re not really brown, maybe they’re a little bit hazel…”

Last night on Mad Men, the Sterling Cooper crew were watching a dog food focus group. The owners start describing their dogs’ personalities, and one of the guys from creative exclaims, “They’re not describing their dogs, they’re describing themselves!”.

To which Don replied, “Is this your first focus group?”

Pretty much the same story. We project onto our genes what we want ourselves to be – and what we want most is to fit the expected value.