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25-Oct-2019 21:31

We find that the MFSD12 region shows significant evidence of selection in East Asians (dated after their split from Europeans) and that the frequency of the Y182H variant correlates with the intensity of solar radiation.

We also explored the genetic architecture of pigmentation in Latin Americans, and found multiple independent signals of association at the 11q14 and 15q23 regions (overlapping GRM5/TYR and HERC2/OCA2), as well as signals of epistatic interactions among independently associated alleles.

To this end, here we report a genome-wide association study (GWAS) of pigmentation in over 6000 Latin Americans, most with high Native American ancestry.

It is well established that Native Americans are closely related to East Asians, the initial settlement of the New World starting some 15,000 years ago, through migration from Eastern Siberia into North America.

In particular, the observation of a decrease in human skin pigmentation at increasing distance from the Equator has been interpreted as resulting from an adaptation to lower levels of ultraviolet radiation, consistent with the tanning response being a physiological skin-protection mechanism.

As a corollary, it has been suggested that variation in eye and hair color in Western Eurasians could represent a by-product of natural selection on skin pigmentation.

Strongest association with skin pigmentation at 19p13 was observed for an Y182H missense variant (common only in East Asians and Native Americans) in MFSD12, a gene recently associated with skin pigmentation in Africans.

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We found eighteen signals of association at twelve genomic regions.

Overall, our findings highlight the complex genetic architecture of pigmentation phenotypes in Latin Americans, and support the view that, in modern humans, lighter skin pigmentation has evolved independently at least twice in Eurasia, possibly as an adaptation to geographic variation in solar radiation exposure..

Information on skin, hair and eye (iris) pigmentation (Figs. Skin pigmentation, measured using reflectometry by the melanin index (MI), showed extensive variation.

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We identified four novel associated regions involving skin or eye pigmentation.



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