Journal article
A meta-analysis of genome-wide association studies of multiple myeloma among men and women of African ancestry
Blood advances, Vol.4(1), pp.181-190
01/14/2020
DOI: 10.1182/bloodadvances.2019000491
PMCID: PMC6960456
PMID: 31935283
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 x 10(-12)). Our study shows that common genetic variation contributes to MM risk in individuals with AA.
Details
- Title: Subtitle
- A meta-analysis of genome-wide association studies of multiple myeloma among men and women of African ancestry
- Creators
- Zhaohui Du - University of Southern CaliforniaNiels Weinhold - University of Arkansas for Medical SciencesGregory Chi Song - University of Southern CaliforniaKristin A. Rand - University of Southern CaliforniaDavid 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 Dept Hlth, Canc Epidemiol Serv, Epidemiol Environm & Occupat Hlth Div, Trenton, NJ USAEdward S. Peters - Louisiana State UniversityCathryn Bock - Wayne State UniversityAnn Mohrbacher - University of Southern CaliforniaAlexander Stram - University of Southern CaliforniaSonja Berndt - National Institutes of HealthWilliam J. Blot - Vanderbilt UniversityGraham Casey - University of VirginiaVictoria L. Stevens - American Cancer SocietyRick Kittles - City Of Hope National Medical CenterPhyllis J. Goodman - Southwest Oncol Grp Stat Ctr, Seattle, WA USAW. Ryan Diver - American Cancer SocietyAnselm Hennis - Stony Brook UniversityBarbara Nemesure - Stony Brook UniversityEric A. Klein - Cleveland Clin Fdn, 9500 Euclid Ave, Cleveland, OH 44195 USABenjamin A. Rybicki - Henry Ford Health SystemJanet L. Stanford - Fred Hutch Cancer CenterJohn S. Witte - University of California, San FranciscoLisa Signorello - National Institutes of HealthEsther M. John - Stanford UniversityLeslie Bernstein - City Of Hope National Medical CenterAntoinette M. 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 - National Institutes of HealthSarah J. Nyante - University of North Carolina at Chapel HillSue Ann Ingles - University of Southern CaliforniaMichael F. Press - University of Southern CaliforniaJohn David Carpten - University of Southern CaliforniaStephen J. Chanock - National Institutes of HealthJayesh Mehta - Northwestern UniversityGraham A. Colditz - Washington University in St. LouisJeffrey Wolf - University of California, San FranciscoThomas G. Martin - University of California, San FranciscoMichael Tomasson - University of IowaMark A. Fiala - Washington University in St. LouisHoward Terebelo - Ascension Providence HospitalNalini Janakiraman - Henry Ford Health SystemLaurence 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 Stram - University of Southern CaliforniaRavi 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 Health Science Center at HoustonDavid Conti - University of Southern CaliforniaChristopher A. Haiman - University of Southern CaliforniaWendy Cozen - University of Southern California
- Resource Type
- Journal article
- Publication Details
- Blood advances, Vol.4(1), pp.181-190
- DOI
- 10.1182/bloodadvances.2019000491
- PMID
- 31935283
- PMCID
- PMC6960456
- NLM abbreviation
- Blood Adv
- ISSN
- 2473-9529
- eISSN
- 2473-9537
- Publisher
- Elsevier
- Number of pages
- 10
- Grant note
- NCI Surveillance Epidemiology and End Results Population-based Registry Program, NIH, Department of Health and Human Services 1R01CA134786; R01 CA84979; 5U01CA164973; P30CA01409; P50CA100707; R21 CA1918896; R01 CA092447 / NCI, National Institutes of Health (NIH); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) 103885 / California Department of Health Services 1U58DP000807-01 / Centers for Disease Control and Prevention; United States Department of Health & Human Services; Centers for Disease Control & Prevention - USA P30 CA014089 / NCI Comprehensive Cancer Center Core grant P30 CA006973 / NCI Sidney Kimmel Comprehensive Cancer Center core grant; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Language
- English
- Date published
- 01/14/2020
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Health, Sport, and Human Physiology ; Internal Medicine
- Record Identifier
- 9984359681602771
Metrics
31 Record Views