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

PeerJ. 2017 Nov 2:5:e3951. doi: 10.7717/peerj.3951. eCollection 2017.


Background: Currently, 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.

Methods: We 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.

Results: For 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.

Discussion: 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.

Keywords: East Asia; Genome-wide association study; Iris color; Skin pigmentation.

Grants and funding

Lida Rawofi was funded by a Natural Sciences and Engineering Research Council (NSERC) CGS-M scholarship. Esteban J. Parra was funded by an NSERC Discovery Grant. Heather L. Norton and Esteban J. Parra were funded by the US National Institute of Justice (grant 2013-DN-BX-K011). In Canada, computations were performed on the GPC supercomputer at the SciNet HPC Consortium. SciNet is funded by: the Canada Foundation for Innovation under the auspices of Compute Canada; the Government of Ontario; Ontario Research Fund—Research Excellence; and the University of Toronto. Yanyun Ma, Jiucun Wang and Li Jin were funded by grants from the National Science Foundation of China (31521003) the Science and Technology Committee of Shanghai Municipality (16JC1400500) and the 111 project (B13016) from Ministry of Education of P.R.China. Bing Su was funded by grants from the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB13010000) and the National Natural Science Foundation of China (91631306). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.