Browsing by Author "Zhang, Mingfeng"
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Item Open Access Genome-wide association study identifies a new melanoma susceptibility locus at 1q21.3.(Nature genetics, 2011-10-09) Macgregor, Stuart; Montgomery, Grant W; Liu, Jimmy Z; Zhao, Zhen Zhen; Henders, Anjali K; Stark, Mitchell; Schmid, Helen; Holland, Elizabeth A; Duffy, David L; Zhang, Mingfeng; Painter, Jodie N; Nyholt, Dale R; Maskiell, Judith A; Jetann, Jodie; Ferguson, Megan; Cust, Anne E; Jenkins, Mark A; Whiteman, David C; Olsson, Håkan; Puig, Susana; Bianchi-Scarrà, Giovanna; Hansson, Johan; Demenais, Florence; Landi, Maria Teresa; Dębniak, Tadeusz; Mackie, Rona; Azizi, Esther; Bressac-de Paillerets, Brigitte; Goldstein, Alisa M; Kanetsky, Peter A; Gruis, Nelleke A; Elder, David E; Newton-Bishop, Julia A; Bishop, D Timothy; Iles, Mark M; Helsing, Per; Amos, Christopher I; Wei, Qingyi; Wang, Li-E; Lee, Jeffrey E; Qureshi, Abrar A; Kefford, Richard F; Giles, Graham G; Armstrong, Bruce K; Aitken, Joanne F; Han, Jiali; Hopper, John L; Trent, Jeffrey M; Brown, Kevin M; Martin, Nicholas G; Mann, Graham J; Hayward, Nicholas KWe performed a genome-wide association study of melanoma in a discovery cohort of 2,168 Australian individuals with melanoma and 4,387 control individuals. In this discovery phase, we confirm several previously characterized melanoma-associated loci at MC1R, ASIP and MTAP-CDKN2A. We selected variants at nine loci for replication in three independent case-control studies (Europe: 2,804 subjects with melanoma, 7,618 control subjects; United States 1: 1,804 subjects with melanoma, 1,026 control subjects; United States 2: 585 subjects with melanoma, 6,500 control subjects). The combined meta-analysis of all case-control studies identified a new susceptibility locus at 1q21.3 (rs7412746, P = 9.0 × 10(-11), OR in combined replication cohorts of 0.89 (95% CI 0.85-0.95)). We also show evidence suggesting that melanoma associates with 1q42.12 (rs3219090, P = 9.3 × 10(-8)). The associated variants at the 1q21.3 locus span a region with ten genes, and plausible candidate genes for melanoma susceptibility include ARNT and SETDB1. Variants at the 1q21.3 locus do not seem to be associated with human pigmentation or measures of nevus density.Item Open Access Joint effect of multiple common SNPs predicts melanoma susceptibility.(PloS one, 2013-01) Fang, Shenying; Han, Jiali; Zhang, Mingfeng; Wang, Li-e; Wei, Qingyi; Amos, Christopher I; Lee, Jeffrey ESingle genetic variants discovered so far have been only weakly associated with melanoma. This study aims to use multiple single nucleotide polymorphisms (SNPs) jointly to obtain a larger genetic effect and to improve the predictive value of a conventional phenotypic model. We analyzed 11 SNPs that were associated with melanoma risk in previous studies and were genotyped in MD Anderson Cancer Center (MDACC) and Harvard Medical School investigations. Participants with ≥15 risk alleles were 5-fold more likely to have melanoma compared to those carrying ≤6. Compared to a model using the most significant single variant rs12913832, the increase in predictive value for the model using a polygenic risk score (PRS) comprised of 11 SNPs was 0.07(95% CI, 0.05-0.07). The overall predictive value of the PRS together with conventional phenotypic factors in the MDACC population was 0.69 (95% CI, 0.64-0.69). PRS significantly improved the risk prediction and reclassification in melanoma as compared with the conventional model. Our study suggests that a polygenic profile can improve the predictive value of an individual gene polymorphism and may be able to significantly improve the predictive value beyond conventional phenotypic melanoma risk factors.