Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility.

2.50
Hdl Handle:
http://hdl.handle.net/11287/618107
Title:
Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility.
Authors:
Wessel, J. [et al]; Hattersley, Andrew T.; Frayling, Timothy M.; Yaghootkar, Hanieh
Abstract:
Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF=1.4%) with lower FG (β=-0.09±0.01 mmol l(-1), P=3.4 × 10(-12)), T2D risk (OR[95%CI]=0.86[0.76-0.96], P=0.010), early insulin secretion (β=-0.07±0.035 pmolinsulin mmolglucose(-1), P=0.048), but higher 2-h glucose (β=0.16±0.05 mmol l(-1), P=4.3 × 10(-4)). We identify a gene-based association with FG at G6PC2 (pSKAT=6.8 × 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF=20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (β=0.02±0.004 mmol l(-1), P=1.3 × 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.
Citation:
Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility. 2015, 6:5897 Nat Commun
Publisher:
Nature
Journal:
Nature communications
Issue Date:
Jan-2015
URI:
http://hdl.handle.net/11287/618107
DOI:
10.1038/ncomms6897
PubMed ID:
25631608
Additional Links:
http://dx.doi.org/10.1038/ncomms6897
Note:
This article is freely available via Open Access. Click on the 'Additional Link' above to access the full-text.
Type:
Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.
Language:
en
ISSN:
2041-1723
Appears in Collections:
2015 RD&E publications; Diabetes/Endocrine Services; Honorary contracts publications

Full metadata record

DC FieldValue Language
dc.contributor.authorWessel, J. [et al]en
dc.contributor.authorHattersley, Andrew T.en
dc.contributor.authorFrayling, Timothy M.en
dc.contributor.authorYaghootkar, Haniehen
dc.date.accessioned2016-08-09T11:37:53Z-
dc.date.available2016-08-09T11:37:53Z-
dc.date.issued2015-01-
dc.identifier.citationLow-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility. 2015, 6:5897 Nat Communen
dc.identifier.issn2041-1723-
dc.identifier.pmid25631608-
dc.identifier.doi10.1038/ncomms6897-
dc.identifier.urihttp://hdl.handle.net/11287/618107-
dc.description.abstractFasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF=1.4%) with lower FG (β=-0.09±0.01 mmol l(-1), P=3.4 × 10(-12)), T2D risk (OR[95%CI]=0.86[0.76-0.96], P=0.010), early insulin secretion (β=-0.07±0.035 pmolinsulin mmolglucose(-1), P=0.048), but higher 2-h glucose (β=0.16±0.05 mmol l(-1), P=4.3 × 10(-4)). We identify a gene-based association with FG at G6PC2 (pSKAT=6.8 × 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF=20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (β=0.02±0.004 mmol l(-1), P=1.3 × 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.en
dc.language.isoenen
dc.publisherNatureen
dc.relation.urlhttp://dx.doi.org/10.1038/ncomms6897en
dc.rightsArchived with thanks to Nature Communicationsen
dc.subjectWessex Classification Subject Headings::Endocrinology::Diabetesen
dc.titleLow-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility.en
dc.typeJournal Articleen
dc.typeResearch Support, N.I.H., Extramuralen
dc.typeResearch Support, N.I.H., Intramuralen
dc.typeResearch Support, Non-U.S. Gov'ten
dc.typeResearch Support, U.S. Gov't, P.H.S.en
dc.identifier.journalNature communicationsen
dc.description.noteThis article is freely available via Open Access. Click on the 'Additional Link' above to access the full-text.en
dc.type.versionPublisheden

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