A Meta-Analysis of Genome-Wide Association Studies of Multiple Myeloma among Men and Women of African Ancestry

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Citation

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., et al. (2020). A Meta-Analysis of Genome-Wide Association Studies of Multiple Myeloma among Men and Women of African Ancestry. Blood Advances, 4(1), 181-190. PMCID: PMC6960456

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 x 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 x 10-12). Our study shows that common genetic variation contributes to MM risk in individuals with AA.

URL

http://dx.doi.org/10.1182/bloodadvances.2019000491

Reference Type

Journal Article

Year Published

2020

Journal Title

Blood Advances

Author(s)

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 H.
Mohrbacher, Ann F.
Stram, Alexander
Berndt, Sonja I.
Blot, William J.
Casey, Graham
Stevens, Victoria L.
Kittles, Rick A.
Goodman, Phyllis J.
Diver, W. Ryan
Hennis, Anselm J.
Nemesure, Barbara
Klein, Eric A.
Rybicki, Benjamin A.
Stanford, Janet L.
Witte, John S.
Signorello, Lisa B.
John, Esther M.
Bernstein, Leslie
Stroup, Antoinette M.
Stephens, Owen W.
Zangari, Maurizio
Van Rhee, Frits
Olshan, Andrew F.
Zheng, Wei
Hu, Jennifer J.
Ziegler, Regina G.
Nyante, Sarah J.
Ingles, Sue Ann
Press, Michael F.
Carpten, John
Chanock, Stephen J.
Mehta, Jayesh
Colditz, Graham A.
Wolf, Jeffrey L.
Martin, Thomas G.
Tomasson, Michael H.
Fiala, Mark A.
Terebelo, Howard R.
Janakiraman, Nalini
Kolonel, Laurence N.
Anderson, Kenneth C.
Le Marchand, Loic
Auclair, Daniel
Chiu, Brian C-H.
Ziv, Elad
Stram, Daniel O.
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

Article Type

Regular

PMCID

PMC6960456

Data Set/Study

African American Multiple Myeloma Study
Multiethnic Cohort (MEC) Study
Multiple Myeloma Research Consortium
African Ancestry Breast Cancer Consortium
African Ancestry Prostate Cancer Consortium

Continent/Country

Nonspecific

Race/Ethnicity

African Ancestry

ORCiD

Olshan - 0000-0001-9115-5128