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

被引：370

作者：

Han, Jiali ^{[1
,2
,3
]}

Kraft, Peter ^{[3
,4
]}

Nan, Hongmei ^{[1
,2
,3
,4
]}

Guo, Qun ^{[1
,2
,3
]}

Chen, Constance ^{[5
,6
]}

Qureshi, Abrar ^{[1
,2
]}

Hankinson, Susan E. ^{[1
,2
]}

Hu, Frank B. ^{[1
,2
,4
,7
]}

Duffy, David L. ^{[8
]}

Zhao, Zhen Zhen ^{[8
]}

Martin, Nicholas G. ^{[8
]}

Montgomery, Grant W. ^{[8
]}

Hayward, Nicholas K. ^{[8
]}

Thomas, Gilles ^{[5
]}

Hoover, Robert N. ^{[5
]}

Chanock, Stephen ^{[5
]}

Hunter, David J. ^{[1
,2
,3
,4
,5
,9
,10
]}

机构：

[1] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Boston, MA USA

[3] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA

[4] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[5] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA

[6] BioInformed, Gaithersburg, MD USA

[7] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA

[8] Queensland Inst Med Res, Brisbane, Qld 4006, Australia

[9] Broad Inst Harvard, Cambridge, MA USA

[10] MIT, Cambridge, MA 02139 USA

来源：

PLOS GENETICS | 2008年 / 4卷 / 05期

关键词：

D O I：

10.1371/journal.pgen.1000074

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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

引用

页数：11

共 31 条

[31] A genome-wide scan for naevus count: linkage to CDKN2A and to other chromosome regions
Zhu, Gu
Montgomery, Grant W.
James, Michael R.
Trent, Jeff M.
Hayward, Nicholas K.
Martin, Nicholas G.
Duffy, David L.
[J]. EUROPEAN JOURNAL OF HUMAN GENETICS, 2007, 15 (01) : 94 - 102

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