Genome-wide association study identifies variants at 9p21 and 22q13 associated with development of cutaneous nevi.
Genome-wide association study identifies variants at 9p21 and 22q13 associated with development of cutaneous nevi.
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DOI：
10.1038/ng.410
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发表时间：
2009-08
期刊：
影响因子：
30.8
通讯作者：
Spector, Timothy D.
中科院分区：
文献类型：
--
作者：
Falchi, Mario;Bataille, Veronique;Hayward, Nicholas K.;Duffy, David L.;Bishop, Julia A. Newton;Pastinen, Tomi;Cervino, Alessandra;Zhao, Zhen Z.;Deloukas, Panos;Soranzo, Nicole;Elder, David E.;Barrett, Jennifer H.;Martin, Nicholas G.;Bishop, D. Timothy;Montgomery, Grant W.;Spector, Timothy D.
大量的黑色素细胞痣是皮肤黑色素瘤最重要的已知危险因素。我们在1，524对双胞胎中使用297，108个tag-SNP进行了痣计数的全基因组关联研究，并在4，107名受试者的独立队列中验证了我们的结果。我们在MTAP中发现了强相关的变异体，MTAP是一个与家族性黑色素瘤易感基因CDKN 2A相邻的基因，位于9 p21（rs 4636294，P = 3.4 × 10-15）。进一步在22q13.1（rs 2284063，P = 3.4 × 10-8）定位PLA 2G 6。两项独立研究的3,131例黑色素瘤病例中，这两个基因座也与黑色素瘤风险相关（rs 10757257和rs 132985的比值比为1.23）。大约每11个受试者中就有一个在两个基因座上都是变异纯合的，与保护性等位基因纯合的受试者相比，痣的数量是其两倍，患黑色素瘤的风险也是其两倍。这些数据为常见的黑色素瘤等位基因提供了第一个证据，其作用是通过痣数量介导的。
High number of melanocytic nevi is the most important known risk factor for cutaneous melanoma. We conducted a genome-wide association study for nevus count using 297,108 tag-SNPs in 1,524 twins and validated our results in an independent cohort of 4,107 subjects. We identified strongly associated variants in MTAP, a gene adjacent to the familial melanoma susceptibility locus CDKN2A on 9p21 (rs4636294, P = 3.4 × 10-15). We further identified PLA2G6 on 22q13.1 (rs2284063, P = 3.4 × 10-8). Both loci were also associated with melanoma risk in 3,131 melanoma cases from two independent studies (odds-ratios 1.23 at rs10757257 and rs132985). About one subject in 11 is homozygous for the variant at both loci with twice the number of nevi compared to those homozygous for the protective alleles, and double the risk for melanoma. These data provide the first evidence for common melanoma alleles whose effects are mediated through nevus number.
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影响因子：
9.8
作者：
Chen, Wei-Min;Abecasis, Goncalo R.
通讯作者：
Abecasis, Goncalo R.
影响因子：
8.8
作者：
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影响因子：
3.5
作者：
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通讯作者：
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影响因子：
10.3
作者：
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通讯作者：
Spector, TD
影响因子：
30.8
作者：
Prokopenko I;Langenberg C;Florez JC;Saxena R;Soranzo N;Thorleifsson G;Loos RJ;Manning AK;Jackson AU;Aulchenko Y;Potter SC;Erdos MR;Sanna S;Hottenga JJ;Wheeler E;Kaakinen M;Lyssenko V;Chen WM;Ahmadi K;Beckmann JS;Bergman RN;Bochud M;Bonnycastle LL;Buchanan TA;Cao A;Cervino A;Coin L;Collins FS;Crisponi L;de Geus EJ;Dehghan A;Deloukas P;Doney AS;Elliott P;Freimer N;Gateva V;Herder C;Hofman A;Hughes TE;Hunt S;Illig T;Inouye M;Isomaa B;Johnson T;Kong A;Krestyaninova M;Kuusisto J;Laakso M;Lim N;Lindblad U;Lindgren CM;McCann OT;Mohlke KL;Morris AD;Naitza S;Orrù M;Palmer CN;Pouta A;Randall J;Rathmann W;Saramies J;Scheet P;Scott LJ;Scuteri A;Sharp S;Sijbrands E;Smit JH;Song K;Steinthorsdottir V;Stringham HM;Tuomi T;Tuomilehto J;Uitterlinden AG;Voight BF;Waterworth D;Wichmann HE;Willemsen G;Witteman JC;Yuan X;Zhao JH;Zeggini E;Schlessinger D;Sandhu M;Boomsma DI;Uda M;Spector TD;Penninx BW;Altshuler D;Vollenweider P;Jarvelin MR;Lakatta E;Waeber G;Fox CS;Peltonen L;Groop LC;Mooser V;Cupples LA;Thorsteinsdottir U;Boehnke M;Barroso I;Van Duijn C;Dupuis J;Watanabe RM;Stefansson K;McCarthy MI;Wareham NJ;Meigs JB;Abecasis GR
通讯作者：
Abecasis GR