Genome-wide association study of pigmentary traits (skin and iris color) in individuals of East Asian ancestry.

Lida Rawofi,Heather L Norton,S Krithika,Zhaohui Yang,Jiucun Wang,Yanyun Ma,Melissa Edwards,Bing Su,David Cha,Phuong Le,Esteban J Parra,Li Jin

doi:10.7717/peerj.3951

Abstract

BackgroundCurrently, there is limited knowledge about the genetics underlying pigmentary traits in East Asian populations. Here, we report the results of the first genome-wide association study of pigmentary traits (skin and iris color) in individuals of East Asian ancestry.MethodsWe obtained quantitative skin pigmentation measures (M-index) in the inner upper arm of the participants using a portable reflectometer (N = 305). Quantitative measures of iris color (expressed as L*, a* and b* CIELab coordinates) were extracted from high-resolution iris pictures (N = 342). We also measured the color differences between the pupillary and ciliary regions of the iris (e.g., iris heterochromia). DNA samples were genotyped with Illumina’s Infinium Multi-Ethnic Global Array (MEGA) and imputed using the 1000 Genomes Phase 3 samples as reference haplotypes.ResultsFor skin pigmentation, we did not observe any genome-wide significant signal. We followed-up in three independent Chinese samples the lead SNPs of five regions showing multiple common markers (minor allele frequency ≥ 5%) with good imputation scores and suggestive evidence of association (p-values < 10−5). One of these markers, rs2373391, which is located in an intron of the ZNF804B gene on chromosome 7, was replicated in one of the Chinese samples (p = 0.003). For iris color, we observed genome-wide signals in the OCA2 region on chromosome 15. This signal is driven by the non-synonymous rs1800414 variant, which explains 11.9%, 10.4% and 6% of the variation observed in the b*, a* and L* coordinates in our sample, respectively. However, the OCA2 region was not associated with iris heterochromia.DiscussionAdditional genome-wide association studies in East Asian samples will be necessary to further disentangle the genetic architecture of pigmentary traits in East Asian populations.

Highlights

Human pigmentation diversity is primarily driven by the type, amount and distribution of melanin in the skin, hair and iris
We describe the results of a genome-wide association study of pigmentary traits in East Asian populations
The magnitude of the skin pigmentation effect observed in our study is quite similar to the effects described in previous reports in which the M-index was used to describe constitutive pigmentation (e.g., Edwards et al, 2010, beta = −1.26 in a sample of individuals of East Asian ancestry living in Canada, and beta = −0.86 in a Han Chinese sample; Eaton et al, 2015, beta = −0.91 in a sample of individuals of East Asian ancestry living in Canada)

Summary

Introduction

Human pigmentation diversity is primarily driven by the type, amount and distribution of melanin in the skin, hair and iris. In East Asia two non-synonymous variants in the OCA2 gene; rs1800414 (His615Arg) and rs74653330 (Ala481Thr) have been associated with light skin and eye color (Edwards et al, 2010; Abe et al, 2013; Eaton et al, 2015; Edwards et al, 2016; Norton et al, 2016; Yang et al, 2016). We report the results of the first genome-wide association study of pigmentary traits (skin and iris color) in individuals of East Asian ancestry. Additional genome-wide association studies in East Asian samples will be necessary to further disentangle the genetic architecture of pigmentary traits in East Asian populations

Methods

Results

Discussion

Conclusion