TY - JOUR
T1 - Genome-wide interaction with selected type 2 diabetes 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 D.E.R.I.
AU - Taylor, Kent D.
AU - Rich, Stephen S.
AU - Wagenknecht, Lynne E.
AU - Freedman, Barry I.
AU - Bowden, Donald W.
N1 - Publisher Copyright:
© 2017, World Scientific Publishing Co. Pte. Ltd. All rights reserved.
PY - 2017
Y1 - 2017
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 known T2D loci implicated in insulin secretion. To test this hypothesis, single nucleotide polymorphisms (SNPs) nominally associated with acute insulin response to glucose (AIR g ), a dynamic measure of first-phase insulin secretion, and previously associated with T2D in genome-wide association studies (GWAS) 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 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 (P interaction < 5'10 -6 ) interactions were observed at several loci including DGKB (rs978989), CDK18 (rs12126276), CXCL12 (rs7921850), HCN1 (rs6895191), FAM98A (rs1900780), and MGMT (rs568530). Notable beta-cell GRS interactions included two SNPs at the DGKB locus (rs6976381; rs6962498). 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 known T2D loci implicated in insulin secretion. To test this hypothesis, single nucleotide polymorphisms (SNPs) nominally associated with acute insulin response to glucose (AIR g ), a dynamic measure of first-phase insulin secretion, and previously associated with T2D in genome-wide association studies (GWAS) 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 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 (P interaction < 5'10 -6 ) interactions were observed at several loci including DGKB (rs978989), CDK18 (rs12126276), CXCL12 (rs7921850), HCN1 (rs6895191), FAM98A (rs1900780), and MGMT (rs568530). Notable beta-cell GRS interactions included two SNPs at the DGKB locus (rs6976381; rs6962498). 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 - 10.1142/9789813207813_0024
DO - 10.1142/9789813207813_0024
M3 - Conference article
C2 - 27896979
AN - SCOPUS:85021860153
SN - 2335-6928
VL - 0
SP - 242
EP - 253
JO - Pacific Symposium on Biocomputing
JF - Pacific Symposium on Biocomputing
IS - 212679
T2 - 22nd Pacific Symposium on Biocomputing, PSB 2017
Y2 - 4 January 2017 through 8 January 2017
ER -
