Abstract
Abstract PR05: A meta-analysis of genome-wide association study and eQTL analysis of multiple myeloma among African Americans
Cancer epidemiology, biomarkers & prevention, Vol.29(6_Supplement_2), pp.PR05-PR05
06/01/2020
DOI: 10.1158/1538-7755.DISP19-PR05
Abstract
Abstract
Background: Persons of African ancestry (AA) experience a 1.5-2-fold risk of multiple myeloma (MM) compared to persons of European ancestry (EA). We assembled a set of MM patients with self-reported AA in order to evaluate the contribution of genetics to etiology in this high-risk group.
Methods: Here we present the results of a meta-analysis of two GWAS in 1,813 cases and 8,871 controls of AA. We also conducted an admixture mapping scan to identify risk alleles associated with local ancestry, 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. Finally, we conducted an eQTL analysis measuring gene expression in those genes harboring a risk variant in malignant plasma cells from 292 of the patients from a single site.
Results: In GWAS analysis, we identified two suggestive novel loci located at 9p24.3 and 9p13.1 at P<1 × 10-6, but 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. 20 of the 23 known EA risk variants showed directional consistency and 9 replicated at P<0.05 in AA individuals. In eight regions, we identified markers that better capture MM risk in persons of AA. AA individuals with a PRS in the top 10% had a 1.82-fold (95%CI: 1.56, 2.11) increased MM risk compared to 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).
Conclusion: Our study shows that common genetic variation contributes to MM risk individuals of AA.
This abstract is also being presented as Poster C040.
Citation Format: Zhaohui Du, Niels Weinhold, Gregory Chi Song, Kristen A. Rand, David J. Van Den Berg, Amie E. Hwang, Xin Sheng, Victor Hom, Sikander Ailawadhi, Ajay K. Nooka, Seema Singhal, Karen Pawlish, Edward Peters, Cathryn Bock, Ann Mohrbacher, Alexander Stram, Sonja I. Berndt, William J. Blot, Graham Casey, Victoria L. Stevens, Rick Kittles, Phyllis J. Goodman, W. Ryan Diver, Anselm Hennis, Barbara Nemesure, Eric A. Klein, Benjamin A. Rybicki, Janet L. Stanford, John S. Witte, Lisa Signorello, Esther M. John, Leslie Bernstein, Antoinette Stroup, Owen W. Stephens, Maurizio Zangari, Frits Van Rhee, Andrew Olshan, Wei Zheng, Jennifer J. Hu, Regina Ziegler, Sarah J. Nyante, Sue Ann Ingles, Michael Press, John David Carpten, Stephen Chanock, Jayesh Mehta, Graham A Colditz, Jeffrey Wolf, Thomas G. Martin, Michael Tomasson, Mark A. Fiala, Howard Terebelo, Nalini Janakiraman, Laurence Kolonel, Kenneth C. Anderson, Loic Le Marchand, Daniel Auclair, Brian C.-H. Chiu, Elad Ziv, Daniel Stram, Ravi Vij, Leon Bernal-Mizrachi, Gareth J. Morgan, Jeffrey A. Zonder, Carol Ann Huff, Sagar Lonial, Robert Z. Orlowski, David V. Conti, Christopher A. Haiman, Wendy Cozen. A meta-analysis of genome-wide association study and eQTL analysis of multiple myeloma among African Americans [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr PR05.
Details
- Title: Subtitle
- Abstract PR05: A meta-analysis of genome-wide association study and eQTL analysis of multiple myeloma among African Americans
- Creators
- Zhaohui Du - University of Southern CaliforniaNiels Weinhold - University of Arkansas for Medical SciencesGregory Chi Song - University of Arkansas for Medical SciencesKristen A. RandDavid J. Van Den Berg - University of Southern CaliforniaAmie E. Hwang - University of Southern CaliforniaXin Sheng - University of Southern CaliforniaVictor Hom - University of Southern CaliforniaSikander Ailawadhi - Mayo ClinicAjay K. Nooka - Emory UniversitySeema Singhal - Northwestern UniversityKaren Pawlish - New Jersey Department of HealthEdward Peters - Louisiana State UniversityCathryn Bock - Wayne State UniversityAnn Mohrbacher - University of Southern CaliforniaAlexander StramSonja I. Berndt - United States Department of Health and Human ServicesWilliam J. Blot - Vanderbilt UniversityGraham Casey - University of VirginiaVictoria L. Stevens - American Cancer SocietyRick Kittles - City Of Hope National Medical CenterPhyllis J. GoodmanW. Ryan Diver - University of VirginiaAnselm Hennis - Stony Brook UniversityBarbara Nemesure - Stony Brook UniversityEric A. KleinBenjamin A. Rybicki - Henry Ford HospitalJanet L. Stanford - City Of Hope National Medical CenterJohn S. Witte - University of California, San FranciscoLisa Signorello - United States Department of Health and Human ServicesEsther M. John - Stanford UniversityLeslie Bernstein - City Of Hope National Medical CenterAntoinette Stroup - Rutgers, The State University of New JerseyOwen W. Stephens - University of Arkansas for Medical SciencesMaurizio Zangari - University of Arkansas for Medical SciencesFrits Van Rhee - University of Arkansas for Medical SciencesAndrew Olshan - University of North Carolina at Chapel HillWei Zheng - Vanderbilt UniversityJennifer J. Hu - University of MiamiRegina Ziegler - United States Department of Health and Human ServicesSarah J. Nyante - University of North Carolina at Chapel HillSue Ann Ingles - University of Southern CaliforniaMichael Press - University of Southern CaliforniaJohn David Carpten - University of Southern CaliforniaStephen Chanock - United States Department of Health and Human ServicesJayesh Mehta - Northwestern UniversityGraham A Colditz - Washington University in St. LouisJeffrey Wolf - University of California, San FranciscoThomas G. MartinMichael Tomasson - University of IowaMark A. Fiala - Washington University in St. LouisHoward Terebelo - Ascension Providence HospitalNalini Janakiraman - Henry Ford HospitalLaurence Kolonel - University of Hawaii SystemKenneth C. Anderson - Harvard UniversityLoic Le Marchand - University of Hawaii SystemDaniel Auclair - Multiple Myeloma Research FoundationBrian C.-H. Chiu - University of ChicagoElad Ziv - University of California, San FranciscoDaniel StramRavi Vij - Washington University in St. LouisLeon Bernal-Mizrachi - Emory UniversityGareth J. Morgan - New York UniversityJeffrey A. Zonder - Wayne State UniversityCarol Ann Huff - Johns Hopkins UniversitySagar Lonial - Emory UniversityRobert Z. Orlowski - The University of Texas MD Anderson Cancer CenterDavid V. Conti - University of Southern CaliforniaChristopher A. Haiman - University of Southern CaliforniaWendy Cozen - University of Southern California
- Resource Type
- Abstract
- Publication Details
- Cancer epidemiology, biomarkers & prevention, Vol.29(6_Supplement_2), pp.PR05-PR05
- DOI
- 10.1158/1538-7755.DISP19-PR05
- ISSN
- 1055-9965
- eISSN
- 1538-7755
- Language
- English
- Date published
- 06/01/2020
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Health, Sport, and Human Physiology ; Internal Medicine
- Record Identifier
- 9984363557702771
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