期刊
PLOS ONE
卷 11, 期 7, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0159977
关键词
-
资金
- National Institutes of Health (NIH) [HHSC268200782096C]
- NIH [K99-DK-081350, R01-DK-066358, R01-DK-053591, R01-HL-56266, R01-DK-070941]
- General Clinical Research Center of the WFSM [M01-RR-07122]
- NHLBI [N01-HC-65226]
- National Heart, Lung, and Blood Institute [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, HHSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, HHSN268201300050C]
- National Human Genome Research Institute [U01HG004402]
- National Institutes of Health [HHSN268200625226C, UL1RR025005]
- NIH Roadmap for Medical Research
- University of Alabama at Birmingham [HHSN268201300025C, HHSN268201300026C]
- Northwestern University [HHSN268201300027C]
- University of Minnesota [HHSN268201300028C]
- Kaiser Foundation Research Institute [HHSN268201300029C]
- Johns Hopkins University School of Medicine [HHSN268200900041C]
- Intramural Research Program of the National Institute on Aging
- NHLBI Candidate-gene Association Resource [N01-HC-65226]
- NHGRI Gene Environment Association Studies (GENEVA) [U01-HG004729, U01-HG04424, U01-HG004446]
- National Institute on Minority Health and Health Disparities
- National Heart, Lung, and Blood Institute (NHLBI)
- [R01HL087641]
- [R01HL59367]
- [R01HL086694]
- [N01-HC-95159]
- [N01-HC-95160]
- [N01-HC-95161]
- [N01-HC-95162]
- [N01-HC-95163]
- [N01-HC-95164]
- [N01-HC-95165]
- [N01-HC-95166]
- [N01-HC-95167]
- [N01-HC-95168]
- [N01-HC-95169]
- [UL1-TR-001079]
- [UL1-TR-000040]
- [DK063491]
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 (AIR(g)), 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 (P-interaction<5x10(-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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