TY - JOUR
T1 - Genome-wide interaction with insulin secretion loci reveals novel loci for type 2 diabetes in African Americans
AU - Keaton, Jacob M.
AU - Hellwege, Jacklyn N.
AU - Ng, Maggie C.Y.
AU - Palmer, Nicholette D.
AU - Pankow, James S.
AU - Fornage, Myriam
AU - Wilson, James G.
AU - Correa, Adolfo
AU - Rasmussen-Torvik, Laura J.
AU - Rotter, Jerome I.
AU - Chen, Yii Der I.
AU - Taylor, Kent D.
AU - Rich, Stephen S.
AU - Wagenknecht, Lynne E.
AU - Freedman, Barry I.
AU - Bowden, Donald W.
N1 - Publisher Copyright:
© 2016 Keaton et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2016/7
Y1 - 2016/7
N2 - 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 (Pnoitcaretni<5?10 -6 ) interactions were observed at several loci including LYPLAL1 (rs10746381), CHN2 (rs7796525), and EXOC1 (rs4289500). Notable AIRg GRS interactions were observed with SAMD4A (rs11627203) and UTRN (rs17074194). These data support the hypothesis that additional genetic factors contributing to T2D risk can be identified by interactions with insulin secretion loci.
AB - 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 (Pnoitcaretni<5?10 -6 ) interactions were observed at several loci including LYPLAL1 (rs10746381), CHN2 (rs7796525), and EXOC1 (rs4289500). Notable AIRg GRS interactions were observed with SAMD4A (rs11627203) and UTRN (rs17074194). These data support the hypothesis that additional genetic factors contributing to T2D risk can be identified by interactions with insulin secretion loci.
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U2 - 10.1371/journal.pone.0159977
DO - 10.1371/journal.pone.0159977
M3 - Article
C2 - 27448167
AN - SCOPUS:84979561639
SN - 1932-6203
VL - 11
JO - PloS one
JF - PloS one
IS - 7
M1 - e0159977
ER -
