Genome-Wide Association with Diabetes-Related Traits in the Framingham Heart Study

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dc.contributor.author Meigs, James B en_US
dc.contributor.author Manning, Alisa K en_US
dc.contributor.author Fox, Caroline S en_US
dc.contributor.author Florez, Jose C en_US
dc.contributor.author Liu, Chunyu en_US
dc.contributor.author Cupples, L Adrienne en_US
dc.contributor.author Dupuis, Josée en_US
dc.date.accessioned 2011-12-29T22:21:52Z
dc.date.available 2011-12-29T22:21:52Z
dc.date.copyright 2007 en_US
dc.date.issued 2007-9-19 en_US
dc.identifier.citation Meigs, James B, Alisa K Manning, Caroline S Fox, Jose C Florez, Chunyu Liu, L Adrienne Cupples, Josée Dupuis. "Genome-wide association with diabetes-related traits in the Framingham Heart Study" BMC Medical Genetics 8 (Suppl 1): S16. (2007) en_US
dc.identifier.issn 1471-2350 en_US
dc.identifier.uri http://hdl.handle.net/2144/2561
dc.description.abstract BACKGROUND: Susceptibility to type 2 diabetes may be conferred by genetic variants having modest effects on risk. Genome-wide fixed marker arrays offer a novel approach to detect these variants. METHODS: We used the Affymetrix 100K SNP array in 1,087 Framingham Offspring Study family members to examine genetic associations with three diabetes-related quantitative glucose traits (fasting plasma glucose (FPG), hemoglobin A1c, 28-yr time-averaged FPG (tFPG)), three insulin traits (fasting insulin, HOMA-insulin resistance, and 0–120 min insulin sensitivity index); and with risk for diabetes. We used additive generalized estimating equations (GEE) and family-based association test (FBAT) models to test associations of SNP genotypes with sex-age-age2-adjusted residual trait values, and Cox survival models to test incident diabetes. RESULTS: We found 415 SNPs associated (at p < 0.001) with at least one of the six quantitative traits in GEE, 242 in FBAT (18 overlapped with GEE for 639 non-overlapping SNPs), and 128 associated with incident diabetes (31 overlapped with the 639) giving 736 non-overlapping SNPs. Of these 736 SNPs, 439 were within 60 kb of a known gene. Additionally, 53 SNPs (of which 42 had r2 < 0.80 with each other) had p < 0.01 for incident diabetes AND (all 3 glucose traits OR all 3 insulin traits, OR 2 glucose traits and 2 insulin traits); of these, 36 overlapped with the 736 other SNPs. Of 100K SNPs, one (rs7100927) was in moderate LD (r2 = 0.50) with TCF7L2 (rs7903146), and was associated with risk of diabetes (Cox p-value 0.007, additive hazard ratio for diabetes = 1.56) and with tFPG (GEE p-value 0.03). There were no common (MAF > 1%) 100K SNPs in LD (r2 > 0.05) with ABCC8 A1369S (rs757110), KCNJ11 E23K (rs5219), or SNPs in CAPN10 or HNFa. PPARG P12A (rs1801282) was not significantly associated with diabetes or related traits. CONCLUSION: Framingham 100K SNP data is a resource for association tests of known and novel genes with diabetes and related traits posted at. Framingham 100K data replicate the TCF7L2 association with diabetes. en_US
dc.description.sponsorship National Heart, Lung, and Blood Institute's Framingham Heart Study (N01-HC-25195); National Institutes of Health National Center for Research Resources Shared Instrumentation grant (1S10RR163736-01A1); National Center for Research Resources General Clinical Research Center (M01-RR-01066); American Diabetes Association Career Developement Award; GlaxoSmithKline; Merck; Lilly; National Institutes of Health Research Career Award (K23 DK659678-03) en_US
dc.language.iso en en_US
dc.publisher BioMed Central en_US
dc.rights Copyright 2007 Meigs et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution 2.0 License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. en_US
dc.rights.uri http://creativecommons.org/licenses/by/2.0 en_US
dc.title Genome-Wide Association with Diabetes-Related Traits in the Framingham Heart Study en_US
dc.type article en_US
dc.identifier.doi 10.1186/1471-2350-8-S1-S16 en_US
dc.identifier.pubmedid 17903298 en_US
dc.identifier.pmcid 1995610 en_US

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