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GENOME-WIDE INTERACTION WITH SELECTED TYPE 2 DIABETES LOCI REVEALS NOVEL LOCI FOR TYPE 2 DIABETES IN AFRICAN AMERICANS.

TitleGENOME-WIDE INTERACTION WITH SELECTED TYPE 2 DIABETES LOCI REVEALS NOVEL LOCI FOR TYPE 2 DIABETES IN AFRICAN AMERICANS.
Publication TypeJournal Article
Year of Publication2017
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
JournalPac Symp Biocomput
Volume22
Pagination242-253
Date Published2017
ISSN2335-6936
KeywordsAfrican 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

DOI10.1142/9789813207813_0024
Alternate JournalPac Symp Biocomput
PubMed ID27896979
PubMed Central IDPMC5146756
Grant ListHHSN268201100012C / 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
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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
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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
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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
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R01 HL087641 / HL / NHLBI NIH HHS / United States