Two new pigmentation papers

A Genome-Wide Association Study Identifies Novel Alleles Associated with Hair Color and Skin Pigmentation:

It has been a longstanding hypothesis that human pigmentation is tightly regulated by genetic variation. However, very few genes have been identified that contain common genetic variants associated with human pigmentation. We scanned the genome for genetic variants associated with natural hair color and other pigmentary characteristics in a multi-stage study of more than 10,000 men and women of European ancestry from the United States and Australia. We identified IRF4 and SLC24A4 as loci highly associated with hair color, along with three other regions encompassing known pigmentation genes. Further work is needed to identify the causal variants at these loci. Improved understanding of the genetic determinants of human pigmentation may help identify the molecular mechanisms of pigmentation-associated conditions such as the tanning response and skin cancers.

….Taken together, these four regions explain approximately 21.9% of the residual variation in hair color (black-blond) after adjusting for the top four principal components of genetic variation. (Conversely, after adjusting for these four regions, the top four principal components of genetic variation explain 2.6% of the residual variation in hair color.)….


There are four regions because areas around HERC2/OCA2 and MAPT showed signals. MAPT is also known as AIM1 and SLC45A2, so this makes 3 genes of the potassium-dependent sodium/calcium exchangers implicated in pigmentation (the other is SLC24A5 obviously). They adjusted for the components of genetic variation so as not to be confounded by population stratification (i.e., there was some ethnic variation among their whites and so you don’t have a random mating population).
And p-ter points me to, Two newly identified genetic determinants of pigmentation in Europeans:

We present results from a genome-wide association study for variants associated with human pigmentation characteristics among 5,130 Icelanders, with follow-up analyses in 2,116 Icelanders and 1,214 Dutch individuals. Two coding variants in TPCN2 are associated with hair color, and a variant at the ASIP locus shows strong association with skin sensitivity to sun, freckling and red hair, phenotypic characteristics similar to those affected by well-known mutations in MC1R.

TPCN2 seems to have a blonde/brown hair effect in Europeans. Interestingly Haplotter says there’s a recent selective event in Asians about 2 Mb upstream. p-ter says:

Why has pigmentation been so amenable to mapping, while other traits like height, weight, or most diseases hover at about 2-3% of the variance explained? One possibility is that it’s because pigmentation has been subject to strong recent selection–theory predicts that the initial moves toward an new fitness optimum will be loci of large effects, while the later moves will be smaller. Perhaps since this selective pressure has been so recent, we’re still picking up those initial mutations of large effect that are still segregating in the population?

Posted in Uncategorized