학술논문
A meta-analysis of genome-wide association studies of multiple myeloma among men and women of African ancestry
Document Type
article
Author
Du, Zhaohui; Weinhold, Niels; Song, Gregory Chi; Rand, Kristin A; Van Den Berg, David J; Hwang, Amie E; Sheng, Xin; Hom, Victor; Ailawadhi, Sikander; Nooka, Ajay K; Singhal, Seema; Pawlish, Karen; Peters, Edward S; Bock, Cathryn; Mohrbacher, Ann; Stram, Alexander; Berndt, Sonja I; Blot, William J; Casey, Graham; Stevens, Victoria L; Kittles, Rick; Goodman, Phyllis J; Diver, W Ryan; Hennis, Anselm; Nemesure, Barbara; Klein, Eric A; Rybicki, Benjamin A; Stanford, Janet L; Witte, John S; Signorello, Lisa; John, Esther M; Bernstein, Leslie; Stroup, Antoinette M; Stephens, Owen W; Zangari, Maurizio; Van Rhee, Frits; Olshan, Andrew; Zheng, Wei; Hu, Jennifer J; Ziegler, Regina; Nyante, Sarah J; Ingles, Sue Ann; Press, Michael F; Carpten, John David; Chanock, Stephen J; Mehta, Jayesh; Colditz, Graham A; Wolf, Jeffrey; Martin, Thomas G; Tomasson, Michael; Fiala, Mark A; Terebelo, Howard; Janakiraman, Nalini; Kolonel, Laurence; Anderson, Kenneth C; Le Marchand, Loic; Auclair, Daniel; Chiu, Brian C-H; Ziv, Elad; Stram, Daniel; Vij, Ravi; Bernal-Mizrachi, Leon; Morgan, Gareth J; Zonder, Jeffrey A; Huff, Carol Ann; Lonial, Sagar; Orlowski, Robert Z; Conti, David V; Haiman, Christopher A; Cozen, Wendy
Source
Blood Advances. 4(1)
Subject
Language
Abstract
Persons of African ancestry (AA) have a twofold higher risk for multiple myeloma (MM) compared with persons of European ancestry (EA). Genome-wide association studies (GWASs) support a genetic contribution to MM etiology in individuals of EA. Little is known about genetic risk factors for MM in individuals of AA. We performed a meta-analysis of 2 GWASs of MM in 1813 cases and 8871 controls and conducted an admixture mapping scan to identify risk alleles. We fine-mapped the 23 known susceptibility loci to find markers that could better capture MM risk in individuals of AA and constructed a polygenic risk score (PRS) to assess the aggregated effect of known MM risk alleles. In GWAS meta-analysis, we identified 2 suggestive novel loci located at 9p24.3 and 9p13.1 at P < 1 × 10-6; however, no genome-wide significant association was noted. In admixture mapping, we observed a genome-wide significant inverse association between local AA at 2p24.1-23.1 and MM risk in AA individuals. Of the 23 known EA risk variants, 20 showed directional consistency, and 9 replicated at P < .05 in AA individuals. In 8 regions, we identified markers that better capture MM risk in persons with AA. AA individuals with a PRS in the top 10% had a 1.82-fold (95% confidence interval, 1.56-2.11) increased MM risk compared with those with average risk (25%-75%). The strongest functional association was between the risk allele for variant rs56219066 at 5q15 and lower ELL2 expression (P = 5.1 × 10-12). Our study shows that common genetic variation contributes to MM risk in individuals with AA.