Genome-Wide Interaction with Insulin Secretion Loci Reveals Novel Loci for Type 2 Diabetes in African Americans.
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...
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doaj-5df6ad5593254d4583c07d89e3e1ac1d2020-11-25T01:19:27ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01117e015997710.1371/journal.pone.0159977Genome-Wide Interaction with Insulin Secretion Loci Reveals Novel Loci for Type 2 Diabetes in African Americans.Jacob M KeatonJacklyn N HellwegeMaggie C Y NgNicholette D PalmerJames S PankowMyriam FornageJames G WilsonAdolfo CorreaLaura J Rasmussen-TorvikJerome I RotterYii-Der I ChenKent D TaylorStephen S RichLynne E WagenknechtBarry I FreedmanDonald W BowdenType 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 (Pinteraction<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.http://europepmc.org/articles/PMC4957757?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jacob M Keaton Jacklyn N Hellwege Maggie C Y Ng Nicholette D Palmer James S Pankow Myriam Fornage James G Wilson Adolfo Correa Laura J Rasmussen-Torvik Jerome I Rotter Yii-Der I Chen Kent D Taylor Stephen S Rich Lynne E Wagenknecht Barry I Freedman Donald W Bowden |
spellingShingle |
Jacob M Keaton Jacklyn N Hellwege Maggie C Y Ng Nicholette D Palmer James S Pankow Myriam Fornage James G Wilson Adolfo Correa Laura J Rasmussen-Torvik Jerome I Rotter Yii-Der I Chen Kent D Taylor Stephen S Rich Lynne E Wagenknecht Barry I Freedman Donald W Bowden Genome-Wide Interaction with Insulin Secretion Loci Reveals Novel Loci for Type 2 Diabetes in African Americans. PLoS ONE |
author_facet |
Jacob M Keaton Jacklyn N Hellwege Maggie C Y Ng Nicholette D Palmer James S Pankow Myriam Fornage James G Wilson Adolfo Correa Laura J Rasmussen-Torvik Jerome I Rotter Yii-Der I Chen Kent D Taylor Stephen S Rich Lynne E Wagenknecht Barry I Freedman Donald W Bowden |
author_sort |
Jacob M Keaton |
title |
Genome-Wide Interaction with Insulin Secretion Loci Reveals Novel Loci for Type 2 Diabetes in African Americans. |
title_short |
Genome-Wide Interaction with Insulin Secretion Loci Reveals Novel Loci for Type 2 Diabetes in African Americans. |
title_full |
Genome-Wide Interaction with Insulin Secretion Loci Reveals Novel Loci for Type 2 Diabetes in African Americans. |
title_fullStr |
Genome-Wide Interaction with Insulin Secretion Loci Reveals Novel Loci for Type 2 Diabetes in African Americans. |
title_full_unstemmed |
Genome-Wide Interaction with Insulin Secretion Loci Reveals Novel Loci for Type 2 Diabetes in African Americans. |
title_sort |
genome-wide interaction with insulin secretion loci reveals novel loci for type 2 diabetes in african americans. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2016-01-01 |
description |
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 (Pinteraction<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. |
url |
http://europepmc.org/articles/PMC4957757?pdf=render |
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