A genome-wide association study meta-analysis of clinical fracture in 10,012 African American women.

Autor: Taylor KC; School of Public Health and Information Sciences, University of Louisville, 485 E Gray St., Louisville, KY 40202, USA.; Gillings School of Global Public Health, University of North Carolina at Chapel Hill, 137 E. Franklin St., Chapel Hill, NC 27514, USA., Evans DS; California Pacific Medical Center Research Institute, 550 16th Street, Box 0560, San Francisco, CA 94158-2549, USA., Edwards DRV; Vanderbilt Epidemiology Center, Department of Obstetrics and Gynecology, Vanderbilt Genetics Institute, Vanderbilt University, 2525 West End Avenue, Nashville, TN 37203, USA., Edwards TL; Vanderbilt Genetics Institute, Division of Epidemiology, Department of Medicine, Vanderbilt University, 2525 West End Avenue, Nashville, TN 37203, USA., Sofer T; Department of Biostatistics, University of Washington, UW Tower 15th floor, 4333 Brooklyn Ave NE, Seattle 98105, USA., Li G; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Metropolitan Park East Tower, 1730 Minor Ave, Suite 1360, Seattle, WA 98101, USA., Liu Y; Thurston Arthritis Research Center, University of North Carolina at Chapel Hill, 3300 Thurston Bldg., CB# 7280, Chapel Hill NC 27599-7280, NC, USA., Franceschini N; University of North Carolina at Chapel Hill, 137 E. Franklin St., Chapel Hill, NC 27514, USA., Jackson RD; The Ohio State University, 376 W 10th Avenue, Suite 260, Columbus, OH 43210, USA., Giri A; Vanderbilt Genetics Institute, Division of Epidemiology, Department of Medicine, Vanderbilt University, 2525 West End Avenue, Nashville, TN 37203, USA., Donneyong M; School of Public Health and Information Sciences, University of Louisville, 485 E Gray St., Louisville, KY 40202, USA.; Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, 1620 Tremont St, St 3030, Boston, MA 02120, USA., Psaty B; Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology and Health Services, University of Washington; Group Health Research Institute, Group Health Cooperative, Metropolitan Park East Tower, 1730 Minor Ave, Suite 1360, Seattle, WA 98101, USA., Rotter JI; Institute of Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, 1124 W. Carson Street, Bldg., E-5, Torrance, CA 90502, USA., LaCroix AZ; Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109, USA., Jordan JM; Department of Medicine, University of California at Davis Medical Center, PSSB Building, 4150 V St., Sacramento, CA 95817, USA., Robbins JA; Thurston Arthritis Research Center, University of North Carolina at Chapel Hill, 3300 Thurston Bldg., CB# 7280, Chapel Hill NC 27599-7280, NC, USA., Lewis B; University of Alabama, Medical Towers 614, 1717 11th Avenue South, Birmingham, AL 35205, USA., Stefanick ML; Stanford Prevention Research Center, Stanford University School of Medicine, Medical School Office Building, 1265 Welch Road, Mail Code 5411, Stanford, CA 94305, USA., Liu Y; Wake Forest Baptist Medical Center, Medical Center Boulevard, Winston-Salem, NC 27157, USA., Garcia M; Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, 7201 Wisconsin Ave, Suite 3C309, Bethesda, MD 20892, USA., Harris T; Laboratory of Epidemiology and Population Science, Intramural Research Program, National Institute on Aging, National Institutes of Health, 31 Center Drive, Bethesda, MD 20892, USA., Cauley JA; University of Pittsburgh Graduate School of Public Health, Department of Epidemiology, A510 Crabtree Hall, Pittsburgh, PA 15261, USA., North KE; Carolina Center for Genome Sciences, 250 Bell Tower Dr., Chapel Hill, NC 27514, USA.; Gillings School of Global Public Health, University of North Carolina at Chapel Hill, 137 E. Franklin St., Chapel Hill, NC 27514, USA.
Jazyk: angličtina
Zdroj: Bone reports [Bone Rep] 2016 Aug 27; Vol. 5, pp. 233-242. Date of Electronic Publication: 2016 Aug 27 (Print Publication: 2016).
DOI: 10.1016/j.bonr.2016.08.005
Abstrakt: Background: Osteoporosis is a major public health problem associated with excess disability and mortality. It is estimated that 50-70% of the variation in osteoporotic fracture risk is attributable to genetic factors. The purpose of this hypothesis-generating study was to identify possible genetic determinants of fracture among African American (AA) women in a GWAS meta-analysis.
Methods: Data on clinical fractures (all fractures except fingers, toes, face, skull or sternum) were analyzed among AA female participants in the Women's Health Initiative (WHI) (N = 8155), Cardiovascular Health Study (CHS) (N = 504), BioVU (N = 704), Health ABC (N = 651), and the Johnston County Osteoarthritis Project (JoCoOA) (N = 291). Affymetrix (WHI) and Illumina (Health ABC, JoCoOA, BioVU, CHS) GWAS panels were used for genotyping, and a 1:1 ratio of YRI:CEU HapMap haplotypes was used as an imputation reference panel. We used Cox proportional hazard models or logistic regression to evaluate the association of ~ 2.5 million SNPs with fracture risk, adjusting for ancestry, age, and geographic region where applicable. We conducted a fixed-effects, inverse variance-weighted meta-analysis. Genome-wide significance was set at P < 5 × 10 - 8 .
Results: One SNP, rs12775980 in an intron of SVIL on chromosome 10p11.2, reached genome-wide significance (P = 4.0 × 10 - 8 ). Although this SNP has a low minor allele frequency (0.03), there was no evidence for heterogeneity of effects across the studies (I 2  = 0). This locus was not reported in any previous osteoporosis-related GWA studies. We also interrogated previously reported GWA-significant loci associated with fracture or bone mineral density in our data. One locus ( SMOC1 ) generalized, but overall there was not substantial evidence of generalization. Possible reasons for the lack of generalization are discussed.
Conclusion: This GWAS meta-analysis of fractures in African American women identified a potentially novel locus in the supervillin gene, which encodes a platelet-associated factor and was previously associated with platelet thrombus formation in African Americans. If validated in other populations of African descent, these findings suggest potential new mechanisms involved in fracture that may be particularly important among African Americans.
Databáze: MEDLINE
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