A genome-wide association study identifies novel alleles associated with hair color and skin pigmentation

Jiali Han, Peter Kraft, Hongmei Nan, Qun Guo, Constance Chen, Abrar Qureshi, Susan E. Hankinson, Frank B. Hu, David L. Duffy, Zhen Zhao Zhen, Nicholas G. Martin, Grant W. Montgomery, Nicholas K. Hayward, Gilles Thomas, Robert N. Hoover, Stephen Chanock, David J. Hunter

Research output: Contribution to journalArticle

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=6.0×10-62 and p=7.46×10-127, respectively. The IRF4 SNP was also associated with skin color (p = 6.2×10 -14), eye color (p = 6.1×10-13), and skin tanning response to sunlight (p = 3.9×10-89). 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.

Original languageEnglish (US)
Article numbere1000074
JournalPLoS Genetics
Volume4
Issue number5
DOIs
StatePublished - May 2008
Externally publishedYes

Fingerprint

Hair Color
Skin Pigmentation
Genome-Wide Association Study
hair
skin (animal)
pigmentation
hairs
skin
allele
genome
Alleles
alleles
color
Single Nucleotide Polymorphism
single nucleotide polymorphism
polymorphism
gene
Genes
genes
genome-wide association study

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

Han, J., Kraft, P., Nan, H., Guo, Q., Chen, C., Qureshi, A., ... Hunter, D. J. (2008). A genome-wide association study identifies novel alleles associated with hair color and skin pigmentation. PLoS Genetics, 4(5), [e1000074]. https://doi.org/10.1371/journal.pgen.1000074

A genome-wide association study identifies novel alleles associated with hair color and skin pigmentation. / Han, Jiali; Kraft, Peter; Nan, Hongmei; Guo, Qun; Chen, Constance; Qureshi, Abrar; Hankinson, Susan E.; Hu, Frank B.; Duffy, David L.; Zhen, Zhen Zhao; Martin, Nicholas G.; Montgomery, Grant W.; Hayward, Nicholas K.; Thomas, Gilles; Hoover, Robert N.; Chanock, Stephen; Hunter, David J.

In: PLoS Genetics, Vol. 4, No. 5, e1000074, 05.2008.

Research output: Contribution to journalArticle

Han, J, Kraft, P, Nan, H, Guo, Q, Chen, C, Qureshi, A, Hankinson, SE, Hu, FB, Duffy, DL, Zhen, ZZ, Martin, NG, Montgomery, GW, Hayward, NK, Thomas, G, Hoover, RN, Chanock, S & Hunter, DJ 2008, 'A genome-wide association study identifies novel alleles associated with hair color and skin pigmentation', PLoS Genetics, vol. 4, no. 5, e1000074. https://doi.org/10.1371/journal.pgen.1000074
Han, Jiali ; Kraft, Peter ; Nan, Hongmei ; Guo, Qun ; Chen, Constance ; Qureshi, Abrar ; Hankinson, Susan E. ; Hu, Frank B. ; Duffy, David L. ; Zhen, Zhen Zhao ; Martin, Nicholas G. ; Montgomery, Grant W. ; Hayward, Nicholas K. ; Thomas, Gilles ; Hoover, Robert N. ; Chanock, Stephen ; Hunter, David J. / A genome-wide association study identifies novel alleles associated with hair color and skin pigmentation. In: PLoS Genetics. 2008 ; Vol. 4, No. 5.
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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=6.0×10-62 and p=7.46×10-127, respectively. The IRF4 SNP was also associated with skin color (p = 6.2×10 -14), eye color (p = 6.1×10-13), and skin tanning response to sunlight (p = 3.9×10-89). 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.",
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