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

MedStar author(s):
Citation: Diabetes. 61(6):1642-7, 2012 Jun.PMID: 22474029Institution: MedStar Health Research InstituteForm of publication: Journal ArticleMedline article type(s): Journal Article | Research Support, N.I.H., ExtramuralSubject headings: *Diabetes Mellitus, Type 2/ge [Genetics] | *Genetic Predisposition to Disease | *Population Groups/ge [Genetics] | Adult | Aged | Aged, 80 and over | Alleles | Diabetes Mellitus, Type 2/eh [Ethnology] | Female | Genome-Wide Association Study | Genotype | Humans | Male | Metagenomics | Middle Aged | Risk | Risk FactorsLocal holdings: Available online from MWHC library: 1995 - present (after 3 months), Available in print through MWHC library: 1999 - 2006ISSN:
  • 0012-1797
Name of journal: DiabetesAbstract: 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.All authors: Ambite JL, Buyske S, Buzkova P, Crawford DC, Fesinmeyer MD, Florez JC, Franceschini N, Goodloe RJ, Haessler J, Haiman CA, Hindorff LA, Howard BV, Jackson RD, Kolonel LN, Le Marchand L, Liu S, Manson JE, Meigs JB, Monroe KR, Mukamal KJ, North KE, Pankow JS, Pendergrass SA, Peters U, Shrader P, Spencer KL, Voruganti VS, Wan P, Waters K, Wilkens LRDigital Object Identifier: Date added to catalog: 2013-09-17
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Item type Current library Collection Call number Status Date due Barcode
Journal Article MedStar Authors Catalog Article Available 22474029

Available online from MWHC library: 1995 - present (after 3 months), Available in print through MWHC library: 1999 - 2006

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.

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