A genome-wide association study identifies novel alleles associated with hair color and skin pigmentation.
A genome-wide association study identifies novel alleles associated with hair color and skin pigmentation.
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一项全基因组关联研究确定了与头发颜色和皮肤色素沉着相关的新等位基因。
DOI：
10.1371/journal.pgen.1000074
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发表时间：
2008-05-16
期刊：
影响因子：
4.5
通讯作者：
Hunter, David J.
中科院分区：
文献类型：
--
作者：
Han, Jiali;Kraft, Peter;Nan, Hongmei;Guo, Qun;Chen, Constance;Qureshi, Abrar;Hankinson, Susan E.;Hu, Frank B.;Duffy, David L.;Zhao, Zhen Zhen;Martin, Nicholas G.;Montgomery, Grant W.;Hayward, Nicholas K.;Thomas, Gilles;Hoover, Robert N.;Chanock, Stephen;Hunter, David J.
我们对来自美国和澳大利亚的10，000多名欧洲血统的男性和女性进行了多阶段的全基因组自然发色关联研究。对2,287名女性进行的528,173个单核苷酸多态性（SNP）基因分型的初步分析发现，IRF 4和SLC 24 A4是与头发颜色高度相关的基因座，沿着的还有其他三个包含已知色素沉着基因的区域。我们在另外三项研究的7，028名个体中证实了这些关联。在这四项研究中，SLC 24 A4 rs 12896399和IRF 4 rs 12203592与头发颜色有很强的相关性，p = 6.0×10−62和p = 7.46×10−127。 IRF 4 SNP还与肤色（p = 6.2×10−14）、眼睛颜色（p = 6.1×10−13）和皮肤对阳光的晒黑反应（p = 3.9×10−89）相关。 一项多变量分析汇集了来自最初GWAS和另外1,440名个体的数据，表明rs 12203592与头发颜色之间的关联独立于rs 1540771，rs 1540771是先前发现与头发颜色相关的IRF 4和EXOC 2基因之间的SNP。校正rs 12203592后，rs 1540771与头发颜色之间的关联不显著（p = 0.52）。 MATP基因的一个变异与头发颜色有关。OCA 2基因上游HERC 2基因中的一个变异与头发颜色的关联性最强，与该区域的其他SNPs（包括三个先前报道的SNPs）相比，该变异与头发颜色的关联性最强。在MC 1 R基因周围区域检测到的信号由MC 1 R红发色等位基因解释。我们的研究结果表明，IRF 4和SLC 24 A4基因座与人类的头发颜色和皮肤色素沉着。长期以来，人们一直认为人类的色素沉着受到遗传变异的严格调控。然而，很少有基因已被确定含有与人类色素沉着相关的常见遗传变异。我们在一项多阶段研究中扫描了基因组中与自然发色和其他色素特征相关的遗传变异，该研究涉及来自美国和澳大利亚的10，000多名欧洲血统的男性和女性。我们确定IRF 4和SLC 24 A4与头发颜色高度相关的基因座，沿着的还有其他三个包含已知色素沉着基因的区域。需要进一步的工作，以确定在这些基因座的致病变异。对人类色素沉着的遗传决定因素的进一步了解可能有助于确定色素沉着相关疾病的分子机制，如晒黑反应和皮肤癌。
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. It has been a longstanding hypothesis that human pigmentation is tightly regulated by genetic variation. However, very few genes have been identified that contain common genetic variants associated with human pigmentation. We scanned the genome for genetic variants associated with natural hair color and other pigmentary characteristics in a multi-stage study of more than 10,000 men and women of European ancestry from the United States and Australia. We identified IRF4 and SLC24A4 as loci highly associated with hair color, along with three other regions encompassing known pigmentation genes. Further work is needed to identify the causal variants at these loci. Improved understanding of the genetic determinants of human pigmentation may help identify the molecular mechanisms of pigmentation-associated conditions such as the tanning response and skin cancers.
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影响因子：
64.8
作者：
Frazer, Kelly A.;Ballinger, Dennis G.;Cox, David R.;Hinds, David A.;Stuve, Laura L.;Gibbs, Richard A.;Belmont, John W.;Boudreau, Andrew;Hardenbol, Paul;Leal, Suzanne M.;Pasternak, Shiran;Wheeler, David A.;Willis, Thomas D.;Yu, Fuli;Yang, Huanming;Zeng, Changqing;Gao, Yang;Hu, Haoran;Hu, Weitao;Li, Chaohua;Lin, Wei;Liu, Siqi;Pan, Hao;Tang, Xiaoli;Wang, Jian;Wang, Wei;Yu, Jun;Zhang, Bo;Zhang, Qingrun;Zhao, Hongbin;Zhao, Hui;Zhou, Jun;Gabriel, Stacey B.;Barry, Rachel;Blumenstiel, Brendan;Camargo, Amy;Defelice, Matthew;Faggart, Maura;Goyette, Mary;Gupta, Supriya;Moore, Jamie;Nguyen, Huy;Onofrio, Robert C.;Parkin, Melissa;Roy, Jessica;Stahl, Erich;Winchester, Ellen;Ziaugra, Liuda;Altshuler, David;Shen, Yan;Yao, Zhijian;Huang, Wei;Chu, Xun;He, Yungang;Jin, Li;Liu, Yangfan;Shen, Yayun;Sun, Weiwei;Wang, Haifeng;Wang, Yi;Wang, Ying;Xiong, Xiaoyan;Xu, Liang;Waye, Mary M. Y.;Tsui, Stephen K. W.;Wong, J. Tze-Fei;Galver, Luana M.;Fan, Jian-Bing;Gunderson, Kevin;Murray, Sarah S.;Oliphant, Arnold R.;Chee, Mark S.;Montpetit, Alexandre;Chagnon, Fanny;Ferretti, Vincent;Leboeuf, Martin;Olivier, Jean-Franccois;Phillips, Michael S.;Roumy, Stephanie;Sallee, Clementine;Verner, Andrei;Hudson, Thomas J.;Kwok, Pui-Yan;Cai, Dongmei;Koboldt, Daniel C.;Miller, Raymond D.;Pawlikowska, Ludmila;Taillon-Miller, Patricia;Xiao, Ming;Tsui, Lap-Chee;Mak, William;Song, You Qiang;Tam, Paul K. H.;Nakamura, Yusuke;Kawaguchi, Takahisa;Kitamoto, Takuya;Morizono, Takashi;Nagashima, Atsushi;Ohnishi, Yozo;Sekine, Akihiro;Tanaka, Toshihiro;Tsunoda, Tatsuhiko;Deloukas, Panos;Bird, Christine P.;Delgado, Marcos;Dermitzakis, Emmanouil T.;Gwilliam, Rhian;Hunt, Sarah;Morrison, Jonathan;Powell, Don;Stranger, Barbara E.;Whittaker, Pamela;Bentley, David R.;Daly, Mark J.;de Bakker, Paul I. W.;Barrett, Jeff;Chretien, Yves R.;Maller, Julian;McCarroll, Steve;Patterson, Nick;Pe'er, Itsik;Price, Alkes;Purcell, Shaun;Richter, Daniel J.;Sabeti, Pardis;Saxena, Richa;Schaffner, Stephen F.;Sham, Pak C.;Varilly, Patrick;Altshuler, David;Stein, Lincoln D.;Krishnan, Lalitha;Smith, Albert Vernon;Tello-Ruiz, Marcela K.;Thorisson, Gudmundur A.;Chakravarti, Aravinda;Chen, Peter E.;Cutler, David J.;Kashuk, Carl S.;Lin, Shin;Abecasis, Goncalo R.;Guan, Weihua;Li, Yun;Munro, Heather M.;Qin, Zhaohui Steve;Thomas, Daryl J.;McVean, Gilean;Auton, Adam;Bottolo, Leonardo;Cardin, Niall;Eyheramendy, Susana;Freeman, Colin;Marchini, Jonathan;Myers, Simon;Spencer, Chris;Stephens, Matthew;Donnelly, Peter;Cardon, Lon R.;Clarke, Geraldine;Evans, David M.;Morris, Andrew P.;Weir, Bruce S.;Tsunoda, Tatsuhiko;Johnson, Todd A.;Mullikin, James C.;Sherry, Stephen T.;Feolo, Michael;Skol, Andrew
通讯作者：
Skol, Andrew
影响因子：
2.8
作者：
FRISANCHO, AR;WAINWRIGHT, R;WAY, A
通讯作者：
WAY, A
影响因子：
9.8
作者：
Palmer, JS;Duffy, DL;Sturm, RA
通讯作者：
Sturm, RA
影响因子：
1.7
作者：
CLARK, P;STARK, AE;MARTIN, NG
通讯作者：
MARTIN, NG
影响因子：
4.8
作者：
Du, JY;Fisher, DE
通讯作者：
Fisher, DE