Consistent directions of effect for established type 2 diabetes risk variants across populations: The Population Architecture using Genomics and Epidemiology (PAGE) Consortium

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. MukamalSarah 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

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1642-1647
Number of pages6
JournalDiabetes
Volume61
Issue number6
DOIs
StatePublished - Jun 2012

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