Title | Genome-Wide Interaction with Insulin Secretion Loci Reveals Novel Loci for Type 2 Diabetes in African Americans. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Keaton JM, Hellwege JN, C Y Ng M, Palmer ND, Pankow JS, Fornage M, Wilson JG, Correa A, Rasmussen-Torvik LJ, Rotter JI, Chen Y-DI, Taylor KD, Rich SS, Wagenknecht LE, Freedman BI |
Secondary Authors | Bowden DW |
Journal | PLoS One |
Volume | 11 |
Issue | 7 |
Pagination | e0159977 |
Date Published | 2016 |
ISSN | 1932-6203 |
Keywords | Adult, African Americans, Blood Glucose, Diabetes Mellitus, Type 2, Epistasis, Genetic, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Insulin, Insulin Resistance, Insulin Secretion, Male, Middle Aged, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Reproducibility of Results, Risk Assessment, Risk Factors, Young Adult |
Abstract | Type 2 diabetes (T2D) is the result of metabolic defects in insulin secretion and insulin sensitivity, yet most T2D loci identified to date influence insulin secretion. We hypothesized that T2D loci, particularly those affecting insulin sensitivity, can be identified through interaction with insulin secretion loci. To test this hypothesis, single nucleotide polymorphisms (SNPs) associated with acute insulin response to glucose (AIRg), a dynamic measure of first-phase insulin secretion, were identified in African Americans from the Insulin Resistance Atherosclerosis Family Study (IRASFS; n = 492 subjects). These SNPs were tested for interaction, individually and jointly as a genetic risk score (GRS), using genome-wide association study (GWAS) data from five cohorts (ARIC, CARDIA, JHS, MESA, WFSM; n = 2,725 cases, 4,167 controls) with T2D as the outcome. In single variant analyses, suggestively significant (Pinteraction |
DOI | 10.1371/journal.pone.0159977 |
Alternate Journal | PLoS One |
PubMed ID | 27448167 |
PubMed Central ID | PMC4957757 |
Grant List | U01 DK105556 / DK / NIDDK NIH HHS / United States UL1 TR000124 / TR / NCATS NIH HHS / United States R01 DK087914 / DK / NIDDK NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States R01 DK066358 / DK / NIDDK NIH HHS / United States |