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Consistent directions of effect for established type 2 diabetes risk variants across populations: the population architecture using Genomics and Epidemiology (PAGE) Consortium.


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.

SUBMITTER: Haiman CA 

PROVIDER: S-EPMC3357304 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Consistent directions of effect for established type 2 diabetes risk variants across populations: the population architecture using Genomics and Epidemiology (PAGE) Consortium.

Haiman Christopher A CA   Fesinmeyer Megan D MD   Spencer Kylee L KL   Buzková Petra P   Voruganti V Saroja VS   Wan Peggy P   Haessler Jeff J   Franceschini Nora N   Monroe Kristine R KR   Howard Barbara V BV   Jackson Rebecca D RD   Florez Jose C JC   Kolonel Laurence N LN   Buyske Steven S   Goodloe Robert J RJ   Liu Simin S   Manson Joann E JE   Meigs James B JB   Waters Kevin K   Mukamal Kenneth J KJ   Pendergrass Sarah A SA   Shrader Peter P   Wilkens Lynne R LR   Hindorff Lucia A LA   Ambite Jose Luis JL   North Kari E KE   Peters Ulrike U   Crawford Dana C DC   Le Marchand Loic L   Pankow James S JS  

Diabetes 20120403 6


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 a  ...[more]

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