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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.
Monday,2015-03-09 16:30 America/Los_Angeles — zdrager
| Title | Consistent directions of effect for established type 2 diabetes risk variants across populations: the population architecture using Genomics and Epidemiology (PAGE) Consortium. |
| Publication Type | Journal Article |
| Year of Publication | 2012 |
| Authors | Haiman, CA, Fesinmeyer, MD, Spencer, KL, Bůzková, P, V Voruganti, S, Wan, P, Haessler, J, Franceschini, N, Monroe, KR, Howard, BV, Jackson, RD, Florez, JC, Kolonel, LN, Buyske, S, Goodloe, RJ, Liu, S, Manson, JAE, Meigs, JB, Waters, K, Mukamal, KJ, Pendergrass, SA, Shrader, P, Wilkens, LR, Hindorff, LA, Ambite, JLuis, North, KE, Peters, U, Crawford, DC, Le Marchand, L, Pankow, JS |
| Journal | Diabetes |
| Volume | 61 |
| Issue | 6 |
| Pagination | 1642-7 |
| Date Published | 2012 Jun |
| ISSN | 1939-327X |
| Keywords | Adult, Aged, Aged, 80 and over, Alleles, Diabetes Mellitus, Type 2, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Metagenomics, Middle Aged, Population Groups, Risk, Risk Factors |
| Abstract | <p>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.</p> |
| DOI | 10.2337/db11-1296 |
| Alternate Journal | Diabetes |
| PubMed ID | 22474029 |
| PubMed Central ID | PMC3357304 |
| Grant List | K24 DK080140 / DK / NIDDK NIH HHS / United States P30 CA015704 / CA / NCI NIH HHS / United States U01 HG004790 / HG / NHGRI NIH HHS / United States U01HG004790 / HG / NHGRI NIH HHS / United States U01HG004798 / HG / NHGRI NIH HHS / United States U01HG004801 / HG / NHGRI NIH HHS / United States U01HG004802 / HG / NHGRI NIH HHS / United States U01HG004803 / HG / NHGRI NIH HHS / United States |