Consistent Directions of Effect for Established Type 2 Diabetes Risk Variants Across Populations
The Population Architecture using Genomics and Epidemiology (PAGE) Consortium
- Christopher A. Haiman1⇓,
- Megan D. Fesinmeyer2,
- Kylee L. Spencer3,
- Petra Bůžková4,
- V. Saroja Voruganti5,
- Peggy Wan1,
- Jeff Haessler2,
- Nora Franceschini6,
- Kristine R. Monroe1,
- Barbara V. Howard7,
- Rebecca D. Jackson8,
- Jose C. Florez9,10,11,
- Laurence N. Kolonel12,
- Steven Buyske13,
- Robert J. Goodloe3,
- Simin Liu14,
- JoAnn E. Manson9,15,
- James B. Meigs9,16,
- Kevin Waters1,
- Kenneth J. Mukamal17,
- Sarah A. Pendergrass3,
- Peter Shrader16,
- Lynne R. Wilkens12,
- Lucia A. Hindorff18,
- Jose Luis Ambite19,
- Kari E. North6,
- Ulrike Peters2,
- Dana C. Crawford3,
- Loic Le Marchand12 and
- James S. Pankow20
- 1Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California
- 2Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington
- 3Center for Human Genetics Research, Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee
- 4Department of Biostatistics, University of Washington, Seattle, Washington
- 5Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas
- 6Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina
- 7Medstar Health Research Institute and Georgetown University, Washington, D.C.
- 8Department of Internal Medicine, Ohio State University, Columbus, Ohio
- 9Harvard Medical School, Boston, Massachusetts
- 10Diabetes Unit and Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts
- 11Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts
- 12Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii
- 13Departments of Genetics and Statistics, Rutgers University, Piscataway, New Jersey
- 14Department of Epidemiology, School of Public Health, University of California, Los Angeles, California
- 15Brigham and Women's Hospital, Boston, Massachusetts
- 16General Medicine Division, Massachusetts General Hospital, Boston, Massachusetts
- 17Beth Israel Deaconess Medical Center, Boston, Massachusetts
- 18Office of Population Genomics, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland
- 19Information Sciences Institute, University of Southern California, Los Angeles, California
- 20Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, Minnesota
- Corresponding author: Christopher A. Haiman, .
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 (Pheterogeneity < 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.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db11-1296/-/DC1.
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The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.
- Received September 14, 2011.
- Accepted February 9, 2012.
- © 2012 by the American Diabetes Association.
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