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

作者：Jiali Han, Peter Kraft, Hongmei Nan, Qun Guo, Constance Chen, Abrar A. Qureshi, Susan E. Hankinson, Frank B. Hu, David L. Duffy, Zhen Zhao, Nicholas G. Martin, Grant W. Montgomery, Nicholas K. Hayward, Gilles Thomas, Robert N. Hoover, Stephen Chanock, David J. Hunter · 发表于：PLoS Genetics · 年份：2008 · DOI：10.1371/journal.pgen.1000074 · 被引用次数：515 · 研究领域：melanin and skin pigmentation、Skin Protection and Aging、Dyeing and Modifying Textile Fibers

We conducted a multi-stage genome-wide association study of natural hair color in more than 10,000 men and women of European ancestry from the United States and Australia. An initial analysis of 528,173 single nucleotide polymorphisms (SNPs) genotyped on 2,287 women identified IRF4 and SLC24A4 as loci highly associated with hair color, along with three other regions encompassing known pigmentation genes. We confirmed these associations in 7,028 individuals from three additional studies. Across these four studies, SLC24A4 rs12896399 and IRF4 rs12203592 showed strong associations with hair color, with p = 6.0x10(-62) and p = 7.46x10(-127), respectively. The IRF4 SNP was also associated with skin color (p = 6.2x10(-14)), eye color (p = 6.1x10(-13)), and skin tanning response to sunlight (p = 3.9x10(-89)). A multivariable analysis pooling data from the initial GWAS and an additional 1,440 individuals suggested that the association between rs12203592 and hair color was independent of rs1540771, a SNP between the IRF4 and EXOC2 genes previously found to be associated with hair color. After adjustment for rs12203592, the association between rs1540771 and hair color was not significant (p = 0.52). One variant in the MATP gene was associated with hair color. A variant in the HERC2 gene upstream of the OCA2 gene showed the strongest and independent association with hair color compared with other SNPs in this region, including three previously reported SNPs. The signals detected in a re...