一项在拉丁美洲人群中开展的全基因组关联研究强调了欧亚人群中浅色皮肤色素沉着的趋同进化。

A GWAS in Latin Americans highlights the convergent evolution of lighter skin pigmentation in Eurasia.

机构信息

Department of Genetics, Evolution and Environment, and UCL Genetics Institute, University College London, London, WC1E 6BT, UK.

Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, 31, Peru.

出版信息

Nat Commun. 2019 Jan 21;10(1):358. doi: 10.1038/s41467-018-08147-0.

We report a genome-wide association scan in >6,000 Latin Americans for pigmentation of skin and eyes. We found eighteen signals of association at twelve genomic regions. These include one novel locus for skin pigmentation (in 10q26) and three novel loci for eye pigmentation (in 1q32, 20q13 and 22q12). We demonstrate the presence of multiple independent signals of association in the 11q14 and 15q13 regions (comprising the GRM5/TYR and HERC2/OCA2 genes, respectively) and several epistatic interactions among independently associated alleles. 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. We show that the frequency of the derived allele at Y182H is significantly correlated with lower solar radiation intensity in East Asia and infer that MFSD12 was under selection in East Asians, probably after their split from Europeans.

我们在 6000 多名拉丁美洲人中进行了一项全基因组关联扫描，研究皮肤和眼睛的色素沉着。我们在十二个基因组区域发现了十八个关联信号。其中包括一个皮肤色素沉着的新位点（位于 10q26）和三个眼睛色素沉着的新位点（位于 1q32、20q13 和 22q12）。我们证明了 11q14 和 15q13 区域（分别包含 GRM5/TYR 和 HERC2/OCA2 基因）中存在多个独立的关联信号，以及几个独立关联等位基因之间的上位性相互作用。在 19p13 上与皮肤色素沉着最强相关的是 MFSD12 基因中的 Y182H 错义变体（仅在东亚人和美洲原住民中常见），该基因最近与非洲人的皮肤色素沉着有关。我们表明，Y182H 衍生等位基因的频率与东亚地区太阳辐射强度的降低显著相关，我们推断 MFSD12 在东亚地区受到了选择，可能是在东亚人与欧洲人分离之后。