Consistent Directions of Effect for Established Type 2 Diabetes Risk Variants Across Populations
Year: 2012
Type: article
Study design: Observational Study
Abstract: Common genetic risk variants for type 2 diabetes (T2D) have primarily been identified in populations of European and Asian ancestry. We tested whether the direction of association with 20 T2D risk variants generalizes across six major racial/ethnic groups in the U.S. as part of the Population Architecture using Genomics and Epidemiology Consortium (16,235 diabetes case and 46,122 control subjects of European American, African American, Hispanic, East Asian, American Indian, and Native Hawaiian ancestry). The percentage of positive (odds ratio [OR] >1 for putative risk allele) associations ranged from 69% in American Indians to 100% in European Americans. Of the nine variants where we observed significant heterogeneity of effect by racial/ethnic group (P(heterogeneity) < 0.05), eight were positively associated with risk (OR >1) in at least five groups. The marked directional consistency of association observed for most genetic variants across populations implies a shared functional common variant in each region. Fine-mapping of all loci will be required to reveal markers of risk that are important within and across populations.
Source: Diabetes
DOI: 10.2337/db11-1296
Authors: Christopher A. Haiman, Megan D. Fesinmeyer, Kylee L. Spencer, Petra Bůžková, V. Saroja Voruganti, Peggy Wan, Jeff Haessler, Nora Franceschini, Kristine R. Monroe, Barbara V. Howard, Rebecca D. Jackson, Jose C. Florez, Laurence N. Kolonel, Steven Buyske, Robert J. Goodloe, Simin Liu, JoAnn E. Manson, James B. Meigs, Kevin Waters, Kenneth J. Mukamal, Sarah A. Pendergrass, Peter Shrader, Lynne R. Wilkens, Lucia A. Hindorff, Jose Luis Ambite, Kari E. North, Ulrike Peters, Dana C. Crawford, Loic Le Marchand, James S. Pankow
Institutions: University of Southern California, USC Norris Comprehensive Cancer Center, Fred Hutch Cancer Center, Vanderbilt University, University of Washington, Texas Biomedical Research Institute, University of North Carolina at Chapel Hill, Georgetown University, The Ohio State University, Broad Institute, Harvard University, Massachusetts General Hospital, University of Hawaii Cancer Center, Rutgers, The State University of New Jersey, University of California, Los Angeles, Brigham and Women's Hospital, Beth Israel Deaconess Medical Center, National Institutes of Health, National Human Genome Research Institute, University of Minnesota
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Awards: Epidemiology of putative genuine genetic variant: The Women's Health Intiative, Epidemiology of Putative Causal Variants in the Multiethnic Cohort, NHGRI EpiGenVar Coordinating Center, Epidemiology of Precursors to Type 2 Diabetes, Genetic Epidemiology of Causal Variants Across the Life Course, Epidemiologic Architecture for Genes Linked to Environment (EAGLE), Cancer Center Support Grant
OpenAlex ID: W2109270077