Title | GENOME-WIDE INTERACTION WITH SELECTED TYPE 2 DIABETES LOCI REVEALS NOVEL LOCI FOR TYPE 2 DIABETES IN AFRICAN AMERICANS. |
Publication Type | Journal Article |
Year of Publication | 2017 |
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 | Pac Symp Biocomput |
Volume | 22 |
Pagination | 242-253 |
Date Published | 2017 |
ISSN | 2335-6936 |
Keywords | African Americans, Case-Control Studies, Computational Biology, Diabetes Mellitus, Type 2, Genome-Wide Association Study, Humans, Insulin Resistance, Insulin-Secreting Cells, Polymorphism, Single Nucleotide, Principal Component Analysis, Risk Factors |
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 known T2D loci implicated in insulin secretion. To test this hypothesis, single nucleotide polymorphisms (SNPs) nominally associated with acute insulin response to glucose (AIRg), 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 (Pinteraction |
DOI | 10.1142/9789813207813_0024 |
Alternate Journal | Pac Symp Biocomput |
PubMed ID | 27896979 |
PubMed Central ID | PMC5146756 |
Grant List | HHSN268201100012C / HL / NHLBI NIH HHS / United States HHSN268201100009I / HL / NHLBI NIH HHS / United States HHSN268201300026C / HL / NHLBI NIH HHS / United States N01HC95160 / HL / NHLBI NIH HHS / United States U01 HG004446 / HG / NHGRI NIH HHS / United States R01 DK070941 / DK / NIDDK NIH HHS / United States HHSN268201100010C / HL / NHLBI NIH HHS / United States UL1 RR025005 / RR / NCRR NIH HHS / United States N01HC95163 / HL / NHLBI NIH HHS / United States HHSN268201100008C / HL / NHLBI NIH HHS / United States UL1 TR001079 / TR / NCATS NIH HHS / United States HHSN268201100005G / HL / NHLBI NIH HHS / United States U01 DK105556 / DK / NIDDK NIH HHS / United States HHSN268201100008I / HL / NHLBI NIH HHS / United States R01 HL059367 / HL / NHLBI NIH HHS / United States HHSN268201100007C / HL / NHLBI NIH HHS / United States N01HC95169 / HL / NHLBI NIH HHS / United States HHSN268201100011I / HL / NHLBI NIH HHS / United States HHSN268201100011C / HL / NHLBI NIH HHS / United States R01 HL086694 / HL / NHLBI NIH HHS / United States HHSN268201300048C / HL / NHLBI NIH HHS / United States U01 HG004402 / HG / NHGRI NIH HHS / United States U01 HG004424 / HG / NHGRI NIH HHS / United States N01HC95164 / HL / NHLBI NIH HHS / United States UL1 TR000124 / TR / NCATS NIH HHS / United States HHSN268201300025C / HL / NHLBI NIH HHS / United States N01HC95162 / HL / NHLBI NIH HHS / United States N01HC95168 / HL / NHLBI NIH HHS / United States U01 HG004729 / HG / NHGRI NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States HHSN268201300027C / HL / NHLBI NIH HHS / United States K99 DK081350 / DK / NIDDK NIH HHS / United States HHSN268201100006C / HL / NHLBI NIH HHS / United States HHSN268201300049C / HL / NHLBI NIH HHS / United States R01 DK066358 / DK / NIDDK NIH HHS / United States HHSN268200900041C / HL / NHLBI NIH HHS / United States HHSN268201300028C / HL / NHLBI NIH HHS / United States HHSN268201100005I / HL / NHLBI NIH HHS / United States N01HC95165 / HL / NHLBI NIH HHS / United States N01HC95159 / HL / NHLBI NIH HHS / United States N01HC95161 / HL / NHLBI NIH HHS / United States HHSN268201300047C / HL / NHLBI NIH HHS / United States HHSN268201300050C / HL / NHLBI NIH HHS / United States N01HC65226 / HL / NHLBI NIH HHS / United States M01 RR007122 / RR / NCRR NIH HHS / United States N01HC95167 / HL / NHLBI NIH HHS / United States HHSN268201100009C / HL / NHLBI NIH HHS / United States HHSN268201100005C / HL / NHLBI NIH HHS / United States R01 DK053591 / DK / NIDDK NIH HHS / United States HHSN268201100007I / HL / NHLBI NIH HHS / United States UL1 TR000040 / TR / NCATS NIH HHS / United States HHSN268201300046C / HL / NHLBI NIH HHS / United States N01HC95166 / HL / NHLBI NIH HHS / United States HHSN268201300029C / HL / NHLBI NIH HHS / United States R01 HL087641 / HL / NHLBI NIH HHS / United States |