- 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
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.