A meta-analysis of genome-wide association studies of multiple myeloma among men and women of African ancestry
Open accessAbstract
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.
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Genetic predisposition plays an important role in the initial transformation and is driven by both germline variants and multiple myeloma-specific loci influencing risk.
“Genetic predisposition plays an important role in the initial transformation and is driven by both germline variants and MM-specific loci influencing risk.”
From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [43]
The Introduction (page unavailable) links familial risk and identified susceptibility loci to a genetic contribution to multiple myeloma risk. The Discussion (page unavailable) says the functional basis of most risk variants remains elusive. The paper therefore supports inherited variation and risk loci influencing susceptibility, but does not establish that they drive the initial transformation. (LLM, conf=0.86)
Experimental — accuracy not yet measuredSome SNPs associated with multiple myeloma and MGUS/SMM are enriched in distinct racial groups, such as African-Americans.
“Importantly some of these SNPs are enriched in distinct racial groups (i.e., African-Americans) and might partially explain the observed racial disparity in incidence of MM.43”
From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [43]
The Results (page unavailable) report that three MM risk alleles were more common in people of African ancestry than in people of European ancestry, supporting the frequency difference in the citing sentence. The paper does not establish that these differences explain the racial disparity in MM incidence; its Introduction calls the reasons for that disparity unknown. It does not assess MGUS or SMM risk alleles. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThere are reported disparities in occurrence of precursor conditions and multiple myeloma among racial groups.
“The reported disparities in occurrence of precursor conditions and MM among racial groups highlights the role of predisposition and the need for broader cohort studies.”
From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [43]
The Introduction (page not available) reports that multiple myeloma incidence in the United States is twice as high among people of African ancestry as among those of European ancestry. The paper does not report racial differences in the occurrence of precursor conditions, so that part of the attributed claim is unsupported. (LLM, conf=0.88)
Experimental — accuracy not yet measuredA list of loci specific to multiple myeloma and MGUS/SMM exists.
“The second group included a list of loci that are specific to multiple myeloma and MGUS/SMM .43-46”
From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [43]
The Abstract (page not provided) says the study fine-mapped 23 known multiple myeloma susceptibility loci, supporting the existence of myeloma-associated loci. It does not identify loci specific to MGUS or smoldering multiple myeloma; a search for MGUS found no passage addressing them. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThese SNPs might partially explain the observed racial disparity in incidence of multiple myeloma.
“Importantly some of these SNPs are enriched in distinct racial groups (i.e., African-Americans) and might partially explain the observed racial disparity in incidence of MM.43”
From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [43]
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- Authors
- Du, Z., Weinhold, N., Song, G. C., Rand, K. A., Van Den Berg, D. J., Hwang, A. E., Sheng, X., Hom, V., Ailawadhi, S., Nooka, A. K., Singhal, S., Pawlish, K., Peters, E. S., Bock, C., Mohrbacher, A., Stram, A., Berndt, S. I., Blot, W. J., Casey, G., Stevens, V. L., Kittles, R., Goodman, P. J., Diver, W. R., Hennis, A., Nemesure, B., Klein, E. A., Rybicki, B. A., Stanford, J. L., Witte, J. S., Signorello, L., John, E. M., Bernstein, L., Stroup, A. M., Stephens, O. W., Zangari, M., Van Rhee, F., Olshan, A., Zheng, W., Hu, J. J., Ziegler, R., Nyante, S. J., Ingles, S. A., Press, M. F., Carpten, J. D., Chanock, S. J., Mehta, J., Colditz, G. A., Wolf, J., Martin, T. G., Tomasson, M., Fiala, M. A., Terebelo, H., Janakiraman, N., Kolonel, L., Anderson, K. C., Le Marchand, L., Auclair, D., Chiu, B. C.-H., Ziv, E., Stram, D., Vij, R., Bernal-Mizrachi, L., Morgan, G. J., Zonder, J. A., Huff, C. A., Lonial, S., Orlowski, R. Z., Conti, D. V., Haiman, C. A., & Cozen, W.
- Affiliations
- University of Southern California (US)
- University of Arkansas for Medical Sciences (US)
- Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA;
- Mayo Clinic (US)
- Emory University (US)
- Northwestern University (US)
- New Jersey Department of Health (US)
- Louisiana State University (US)
- Wayne State University (US)
- Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA;
- National Institutes of Health (US)
- Vanderbilt University Medical Center (US)
- University of Virginia (US)
- American Cancer Society (US)
- City Of Hope National Medical Center (US)
- SWOG Cancer Research Network (US)
- Stony Brook University (US)
- Cleveland Clinic (US)
- Henry Ford Hospital (US)
- Fred Hutch Cancer Center (US)
- University of California, San Francisco (US)
- Stanford Medicine (US)
- Rutgers, The State University of New Jersey (US)
- Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, AR;
- University of North Carolina at Chapel Hill (US)
- University of Miami (US)
- Washington University in St. Louis (US)
- University of Iowa (US)
- Ascension Providence Hospital (US)
- University of Hawaii Cancer Center (US)
- Harvard University (US)
- University of Hawaii Cancer Center, Honolulu, HI;
- Multiple Myeloma Research Foundation (US)
- University of Chicago (US)
- Grady Memorial Hospital, Emory University, Atlanta, GA;
- NYU Langone’s Laura and Isaac Perlmutter Cancer Center (US)
- Johns Hopkins University (US)
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Du, Zhaohui
- Weinhold, Niels
- Conti, David V.
- Haiman, Christopher A.
- Cozen, Wendy
- ORCID
- Du, Zhaohui
- Weinhold, Niels
- Rand, Kristin A.
- Hwang, Amie E.
- Sheng, Xin
- Ailawadhi, Sikander
- Nooka, Ajay K.
- Singhal, Seema
- Pawlish, Karen
- Peters, Edward S.
- Bock, Cathryn
- 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.
- John, Esther M.
- Bernstein, Leslie
- Stroup, Antoinette M.
- Stephens, Owen W.
- Zangari, Maurizio
- Olshan, Andrew
- Zheng, Wei
- Hu, Jennifer J.
- Ziegler, Regina
- Nyante, Sarah J.
- Ingles, Sue Ann
- Press, Michael F.
- Carpten, John David
- Chanock, Stephen J.
- Colditz, Graham A.
- Wolf, Jeffrey
- Martin, Thomas G.
- Tomasson, Michael
- Fiala, Mark A.
- Terebelo, Howard
- Kolonel, Laurence
- Anderson, Kenneth C.
- Auclair, Daniel
- Chiu, Brian C.-H.
- Ziv, Elad
- Stram, Daniel
- Vij, Ravi
- Morgan, Gareth J.
- Zonder, Jeffrey A.
- Huff, Carol Ann
- Lonial, Sagar
- Orlowski, Robert Z.
- Conti, David V.
- Haiman, Christopher A.
- Cozen, Wendy
- Venue
- Blood Advances
- Publisher
- American Society of Hematology
- Published
- 2020-01-14
- Volume
- 4
- Issue
- 1
- Pages
- 181-190
- ISSN
- 2473-9529 (ISSN-L)
- 2473-9537
- PMC
- PMC6960456
- OpenAlex
- W2998795209
- Cited by
- 31
- References
- 38
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 4 · 2023: 3 · 2022: 5 · 2021: 5 · 2020: 1
- FWCI
- 0.55
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Blood Advances (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- Civil War Book Review (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (UG1CA233163, R01CA092447, UM1CA182883, UG1CA189974, R21CA191896, U01CA182883, R01CA84979, P50CA100707, R01CA084979, R01CA134786, U10CA037429, P50CA171963, U01CA164973, P30CA014089, P30CA006973)
- National Institute of Environmental Health Sciences (P30ES027792)
- National Center for Chronic Disease Prevention and Health Promotion (U58 DP000807)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P2CHD050924)
- Topics
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Keywords
- multiple myeloma, African ancestry, genetic susceptibility, admixture mapping, polygenic risk score, fine mapping
- MeSH terms
- Female, Humans, Male, Multiple Myeloma, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Transcriptional Elongation Factors, Genome-Wide Association Study, Genetic Loci
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