Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
18483556
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.
DATE PUBLISHED
2008 May
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2007/12/24
accepted 2008/04/14
pubmed 2008/05/17 09:00
medline 2008/06/11 09:00
entrez 2008/05/17 09:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Han J Han Jiali J Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, United States of America.
Kraft P Kraft Peter P
Nan H Nan Hongmei H
Guo Q Guo Qun Q
Chen C Chen Constance C
Qureshi A Qureshi Abrar A
Hankinson SE Hankinson Susan E SE
Hu FB Hu Frank B FB
Duffy DL Duffy David L DL
Zhao ZZ Zhao Zhen Zhen ZZ
Martin NG Martin Nicholas G NG
Montgomery GW Montgomery Grant W GW
Hayward NK Hayward Nicholas K NK
Thomas G Thomas Gilles G
Hoover RN Hoover Robert N RN
Chanock S Chanock Stephen S
Hunter DJ Hunter David J DJ
INVESTIGATORS
JOURNAL
VOLUME: 4
ISSUE: 5
TITLE: PLoS genetics
ISOABBREVIATION: PLoS Genet.
YEAR: 2008
MONTH: May
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1553-7404
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: PLoS Genet
COUNTRY: United States
ISSNLINKING: 1553-7390
NLMUNIQUEID: 101239074
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
CA049449 NCI NIH HHS United States
CA087969 NCI NIH HHS United States
CA098233 NCI NIH HHS United States
CA128080 NCI NIH HHS United States
CA132175 NCI NIH HHS United States
CA88363 NCI NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Alleles
Antiporters genetics
Australia genetics
Case-Control Studies genetics
Cohort Studies genetics
Female genetics
Genome, Human genetics
Genotype genetics
Hair Color genetics
Health Occupations genetics
Humans genetics
Interferon Regulatory Factors genetics
Male genetics
Middle Aged genetics
Polymorphism, Single Nucleotide genetics
Questionnaires genetics
Skin Neoplasms genetics
Skin Pigmentation genetics
United States genetics
Vesicular Transport Proteins genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Antiporters
0 EXOC2 protein, human
0 Interferon Regulatory Factors
0 SLC24A4 protein, human
0 Vesicular Transport Proteins
0 interferon regulatory factor-4
OTHER ID's
OTHERID SOURCE
PMC2367449 NLM