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Genome-Wide Interaction with Insulin Secretion Loci Reveals Novel Loci for Type 2 Diabetes in African Americans.

TitleGenome-Wide Interaction with Insulin Secretion Loci Reveals Novel Loci for Type 2 Diabetes in African Americans.
Publication TypeJournal Article
Year of Publication2016
AuthorsKeaton 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 AuthorsBowden DW
JournalPLoS One
Volume11
Issue7
Paginatione0159977
Date Published2016
ISSN1932-6203
KeywordsAdult, 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

DOI10.1371/journal.pone.0159977
Alternate JournalPLoS One
PubMed ID27448167
PubMed Central IDPMC4957757
Grant ListU01 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