title: A genome-wide association study identifies novel alleles associated with hair color and skin pigmentation.
abstract: 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 region around the MC1R gene were explained by MC1R red hair color alleles. Our results suggest that the IRF4 and SLC24A4 loci are associated with human hair color and skin pigmentation.
authors.affiliation: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Jiali
authors.initials: J
authors.lastname: Han
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.forename: Hongmei
authors.initials: H
authors.lastname: Nan
authors.forename: Qun
authors.initials: Q
authors.lastname: Guo
authors.forename: Constance
authors.initials: C
authors.lastname: Chen
authors.forename: Abrar
authors.initials: A
authors.lastname: Qureshi
authors.forename: Susan E
authors.initials: SE
authors.lastname: Hankinson
authors.forename: Frank B
authors.initials: FB
authors.lastname: Hu
authors.forename: David L
authors.initials: DL
authors.lastname: Duffy
authors.forename: Zhen Zhen
authors.initials: ZZ
authors.lastname: Zhao
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
authors.forename: Grant W
authors.initials: GW
authors.lastname: Montgomery
authors.forename: Nicholas K
authors.initials: NK
authors.lastname: Hayward
authors.forename: Gilles
authors.initials: G
authors.lastname: Thomas
authors.forename: Robert N
authors.initials: RN
authors.lastname: Hoover
authors.forename: Stephen
authors.initials: S
authors.lastname: Chanock
authors.forename: David J
authors.initials: DJ
authors.lastname: Hunter
mesh_terms: D000328:Adult; D000483:Alleles; D017920:Antiporters / Q000235:genetics*; D001315:Australia; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D015894:Genome, Human; D005838:Genotype; D006200:Hair Color / Q000235:genetics*; D006281:Health Occupations; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012878:Skin Neoplasms / Q000235:genetics; D012880:Skin Pigmentation / Q000235:genetics*; D011795:Surveys and Questionnaires; D014481:United States; D033921:Vesicular Transport Proteins / Q000235:genetics; D000099218:Interferon Regulatory Factor-4
chemical_list: D017920:Antiporters; D050835:Interferon Regulatory Factors; D033921:Vesicular Transport Proteins; D000099218:Interferon Regulatory Factor-4; C470182:EXOC2 protein, human; C470570:SLC24A4 protein, human