Abstract
Abstract 223: A meta-analysis of genome-wide association studies of multiple myeloma among African Americans
Cancer research (Chicago, Ill.), Vol.78(13_Supplement), pp.223-223
07/01/2018
DOI: 10.1158/1538-7445.AM2018-223
Abstract
Abstract
Multiple myeloma (MM) is twice as common in African Americans (AA) compared to European Americans (EA). The reported familial clustering and the elevated MM risk among first-degree relatives of cases implicate genetic susceptibility. Previous genome-wide association studies (GWAS) in EA have identified 16 novel risk loci. In this study, we tested the generalizability of the established risk alleles to AA and conducted a meta-GWAS analysis using two sets of AA to identify additional novel common MM risk variants. In the first study, we genotyped 1,305 incident AA MM cases from the African American Multiple Myeloma Study (AAMMS) using the Illumina HumanCore GWAS array and compared them to 7,078 AA controls from the African Ancestry Prostate Cancer Consortium (AAPC) and African Ancestry Breast Cancer Consortium (AABC) using the Illumina 1M-Duo. In the second study, 95 additional AAMMS cases and 435 AA MM cases from the University of Arkansas for Medical Sciences (UAMS) were genotyped using the Illumina MegaBead Chip and compared to 2,390 AA controls from the Multiethnic Cohort. The Haplotype Reference Consortium (HRC) was used to impute the overlapping typed SNPS from each GWAS case and control set together. Per-allele risk associations were tested for 8,715,278 overlapping genotyped and imputed variants with >1% frequency and >0.8 imputation score using unconditional logistic regression in both sets, and the combined effects were estimated using a fixed-effect meta-analysis. Of the 16 reported risk loci discovered in EA, directional consistency was present for 15 variants; eight of these replicated at nominal significance p<0.05, with the most statistically significant variant being rs4487645 at 7p15.3 (OR=1.38, p=3.56×10-6). AA individuals with polygenic risk scores from these 16 variants (PRS) in the top 10% stratum had a 1.44-fold increased MM risk compared to those with a PRS in the 25th -75th percentiles. Additionally, we identified three suggestive novel loci located at 12q12, 9p24.3 and 9p13.1 at p<1×10-6, with ORs ranging from 1.25-1.55, but none reached genome-wide significance. The variant at 9p24.3 is located in an intron in the KANK1 gene and a correlated SNP in EAs (r2=0.5) is strongly associated with gene expression in neoplastic plasma cells (unpublished, Weinhold and Morgan). Our study replicated most of the reported risk loci discovered among EA, demonstrated that a PRS constructed using the 16 reported risk alleles was associated with MM risk, and provides suggestive evidence for additional loci associated with MM risk in AAs.
Citation Format: Zhaohui Du, Chi Song, Kristin Rand, Niels Weinhold, David Van Den Berg, Amie Hwang, Xin Sheng, Victor Hom, Sikander Ailawadhi, Ajay K. Nooka, Seema Singhal, Karen Pawlish, Edward S. Peters, Cathryn Bock, Ann Mohrbacher, Alexander Stram, Sonja I. Berndt, William Blot, John David Carpten, Antoinette Stroup, Andrew Olshan, Wei Zhang, African Ancestry Breast & Prostate Consortium, Stephen Chanock, Jayesh Mehta, Graham A. Colditz, Jeffrey Wolf, Thomas G. Martin, Michael Tomasson, Mark A. Fiala, Howard Terebelo, Nalini Janakiraman, Laurence Kolonel, Loic LeMarchand, 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 studies of multiple myeloma among African Americans [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 223.
Details
- Title: Subtitle
- Abstract 223: A meta-analysis of genome-wide association studies of multiple myeloma among African Americans
- Creators
- Zhaohui Du - USC Norris Comprehensive Cancer CenterChi Song - USC Norris Comprehensive Cancer CenterKristin Rand - University of Southern CaliforniaNiels Weinhold - Myeloma Institute, AR;David Van Den BergAmie Hwang - University of Southern CaliforniaXin Sheng - University of Southern CaliforniaVictor Hom - University of Southern CaliforniaSikander Ailawadhi - Mayo Clinic in ArizonaAjay K. Nooka - Emory UniversitySeema Singhal - Western UniversityKaren Pawlish - New Jersey Department of HealthEdward S. Peters - Louisiana State UniversityCathryn Bock - Wayne State UniversityAnn Mohrbacher - University of Southern CaliforniaAlexander StramSonja I. Berndt - National Cancer Institute, NIH, DHHS, Bethesda, MD.William Blot - International Epidemiology InstituteJohn David Carpten - University of Southern CaliforniaAntoinette Stroup - Rutgers, The State University of New JerseyAndrew Olshan - UNC Gillings School of Public Health, NC;Wei Zhang - Vanderbilt UniversityStephen Chanock - National Cancer Institute, NIH, DHHS, MD;Jayesh Mehta - Western 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 SystemLoic LeMarchandElad Ziv - University of California, San FranciscoDaniel Stram - University of Southern CaliforniaRavi Vij - Washington University in St. LouisLeon Bernal-Mizrachi - Emory UniversityGareth J. Morgan - University of Arkansas at FayettevilleJeffrey A. Zonder - The Barbara Ann Karmanos Cancer InstituteCarol Ann Huff - John Hopkins University, MD;Sagar 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 CaliforniaAfrican Ancestry Breast & Prostate Consortium
- Resource Type
- Abstract
- Publication Details
- Cancer research (Chicago, Ill.), Vol.78(13_Supplement), pp.223-223
- DOI
- 10.1158/1538-7445.AM2018-223
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Language
- English
- Date published
- 07/01/2018
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Health, Sport, and Human Physiology ; Internal Medicine
- Record Identifier
- 9984363274402771
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