| Literature DB >> 31935283 |
Zhaohui Du1, Niels Weinhold2, Gregory Chi Song3, Kristin A Rand3, David J Van Den Berg1, Amie E Hwang3, Xin Sheng1, Victor Hom3, Sikander Ailawadhi4, Ajay K Nooka5, Seema Singhal6, Karen Pawlish7, Edward S Peters8, Cathryn Bock9, Ann Mohrbacher10, Alexander Stram3, Sonja I Berndt11, William J Blot12, Graham Casey13, Victoria L Stevens14, Rick Kittles15, Phyllis J Goodman16, W Ryan Diver14, Anselm Hennis17, Barbara Nemesure17, Eric A Klein18, Benjamin A Rybicki19, Janet L Stanford20, John S Witte21, Lisa Signorello11, Esther M John22, Leslie Bernstein15, Antoinette M Stroup7,23, Owen W Stephens2, Maurizio Zangari2, Frits Van Rhee2, Andrew Olshan24, Wei Zheng12, Jennifer J Hu25, Regina Ziegler11, Sarah J Nyante26, Sue Ann Ingles3, Michael F Press27, John David Carpten28, Stephen J Chanock11, Jayesh Mehta6, Graham A Colditz29, Jeffrey Wolf21, Thomas G Martin21, Michael Tomasson30, Mark A Fiala29, Howard Terebelo31, Nalini Janakiraman32, Laurence Kolonel33, Kenneth C Anderson34, Loic Le Marchand33, Daniel Auclair35, Brian C-H Chiu36, Elad Ziv21, Daniel Stram3, Ravi Vij29, Leon Bernal-Mizrachi37, Gareth J Morgan38, Jeffrey A Zonder9, Carol Ann Huff39, Sagar Lonial5, Robert Z Orlowski40, David V Conti1, Christopher A Haiman1, Wendy Cozen1,27.
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.Entities:
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Year: 2020 PMID： 31935283 PMCID： PMC6960456 DOI： 10.1182/bloodadvances.2019000491
Source DB: PubMed Journal: Blood Adv ISSN： 2473-9529