"A meta-analysis of genome-wide association studies of multiple myeloma" by Zhaohui Du, Niels Weinhold et al.

Faculty Publications

Title

A meta-analysis of genome-wide association studies of multiple myeloma among men and women of African ancestry

Authors

Zhaohui Du, Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA.
Niels Weinhold, Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, AR.
Gregory Chi Song, Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA.
Kristin A. Rand, Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA.
David J. Van Den Berg, Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA.
Amie E. Hwang, Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA.
Xin Sheng, Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA.
Victor Hom, Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA.

Document Type

Article

Publication Date

1-14-2020

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.

Publication Source (Journal or Book title)

Blood advances

First Page

181

Last Page

190

Recommended Citation

Du, Z., Weinhold, N., Song, G. C., Rand, K. A., Van Den Berg, D. J., Hwang, A. E., Sheng, X., & Hom, V. (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. https://doi.org/10.1182/bloodadvances.2019000491

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