Genome-wide association study identifies variants at 9p21 and 22q13 associated with development of cutaneous nevi

被引：158

作者：

Falchi, Mario ^{[1
,2
]}

Bataille, Veronique ^{[1
,3
]}

Hayward, Nicholas K. ^{[4
]}

Duffy, David L. ^{[4
]}

Bishop, Julia A. Newton ^{[5
]}

Pastinen, Tomi ^{[6
,7
]}

Cervino, Alessandra ^{[1
]}

Zhao, Zhen Z. ^{[4
]}

Deloukas, Panos ^{[8
]}

Soranzo, Nicole ^{[1
,8
]}

Elder, David E. ^{[9
]}

Barrett, Jennifer H. ^{[5
]}

Martin, Nicholas G. ^{[4
]}

Bishop, D. Timothy ^{[5
]}

Montgomery, Grant W. ^{[4
]}

Spector, Timothy D. ^{[1
]}

机构：

[1] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England

[2] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, London, England

[3] Hemel Hempstead Gen Hosp, W Hertfordshire NHS Trust, Dept Dermatol, Hemel Hempstead, Herts, England

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

[5] Univ Leeds, Leeds Inst Mol Med, Epidemiol & Biostat Sect, Leeds, W Yorkshire, England

[6] McGill Univ, Dept Human & Med Genet, Montreal, PQ, Canada

[7] Genome Quebec Innovat Ctr, Montreal, PQ, Canada

[8] Wellcome Trust Sanger Inst, Dept Human Genet, Cambridge, England

[9] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

来源：

NATURE GENETICS | 2009年 / 41卷 / 08期

基金：

英国惠康基金;

关键词：

CA2+-INDEPENDENT PHOSPHOLIPASE A(2); METHYLTHIOADENOSINE PHOSPHORYLASE GENE; RISK-FACTORS; CELL-GROWTH; ADULT TWIN; MELANOMA; CANCER; EXPRESSION; PROLIFERATION; INHIBITION;

D O I：

10.1038/ng.410

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

A high melanocytic nevi count is the strongest known risk factor for cutaneous melanoma. We conducted a genome-wide association study for nevus count using 297,108 SNPs in 1,524 twins, with validation in an independent cohort of 4,107 individuals. We identified strongly associated variants in MTAP, a gene adjacent to the familial melanoma susceptibility locus CDKN2A on 9p21 (rs4636294, combined P = 3.4 x 10(-15)), as well as in PLA2G6 on 22q13.1 (rs2284063, combined P = 3.4 x 10(-8)). In addition, variants in these two loci showed association with melanoma risk in 3,131 melanoma cases from two independent studies, including rs10757257 at 9p21, combined P = 3.4 x 10(-8), OR = 1.23 (95% CI = 1.15-1.30) and rs132985 at 22q13.1, combined P = 2.6 x 10(-7), OR = 1.23 (95% CI = 1.15-1.30). This provides the first report of common variants associated to nevus number and demonstrates association of these variants with melanoma susceptibility.

引用

页码：915 / U76

页数：7

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