Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility. / Wessel, Jennifer; Chu, Audrey Y; Willems, Sara M; Wang, Shuai; Yaghootkar, Hanieh; Brody, Jennifer A; Dauriz, Marco; Hivert, Marie-France; Raghavan, Sridharan; Lipovich, Leonard; Hidalgo, Bertha; Fox, Keolu; Huffman, Jennifer E; An, Ping; Lu, Yingchang; Rasmussen-Torvik, Laura J; Grarup, Niels; Ehm, Margaret G; Li, Li; Baldridge, Abigail S; Stančáková, Alena; Abrol, Ravinder; Besse, Céline; Boland, Anne; Bork-Jensen, Jette; Fornage, Myriam; Freitag, Daniel F; Garcia, Melissa E; Guo, Xiuqing; Hara, Kazuo; Isaacs, Aaron; Jakobsdottir, Johanna; Lange, Leslie A; Layton, Jill C; Li, Man; Hua Zhao, Jing; Meidtner, Karina; Morrison, Alanna C; Nalls, Mike A; Peters, Marjolein J; Sabater-Lleal, Maria; Schurmann, Claudia; Silveira, Angela; Smith, Albert V; Southam, Lorraine; Allin, Kristine H; Jørgensen, Torben; Linneberg, Allan; Hansen, Torben; Pedersen, Oluf; EPIC-InterAct Consortium.
I: Nature Communications, Bind 6, 29.01.2015, s. 5897.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility
AU - Wessel, Jennifer
AU - Chu, Audrey Y
AU - Willems, Sara M
AU - Wang, Shuai
AU - Yaghootkar, Hanieh
AU - Brody, Jennifer A
AU - Dauriz, Marco
AU - Hivert, Marie-France
AU - Raghavan, Sridharan
AU - Lipovich, Leonard
AU - Hidalgo, Bertha
AU - Fox, Keolu
AU - Huffman, Jennifer E
AU - An, Ping
AU - Lu, Yingchang
AU - Rasmussen-Torvik, Laura J
AU - Grarup, Niels
AU - Ehm, Margaret G
AU - Li, Li
AU - Baldridge, Abigail S
AU - Stančáková, Alena
AU - Abrol, Ravinder
AU - Besse, Céline
AU - Boland, Anne
AU - Bork-Jensen, Jette
AU - Fornage, Myriam
AU - Freitag, Daniel F
AU - Garcia, Melissa E
AU - Guo, Xiuqing
AU - Hara, Kazuo
AU - Isaacs, Aaron
AU - Jakobsdottir, Johanna
AU - Lange, Leslie A
AU - Layton, Jill C
AU - Li, Man
AU - Hua Zhao, Jing
AU - Meidtner, Karina
AU - Morrison, Alanna C
AU - Nalls, Mike A
AU - Peters, Marjolein J
AU - Sabater-Lleal, Maria
AU - Schurmann, Claudia
AU - Silveira, Angela
AU - Smith, Albert V
AU - Southam, Lorraine
AU - Allin, Kristine H
AU - Jørgensen, Torben
AU - Linneberg, Allan
AU - Hansen, Torben
AU - Pedersen, Oluf
AU - EPIC-InterAct Consortium
PY - 2015/1/29
Y1 - 2015/1/29
N2 - 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.
AB - 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.
U2 - 10.1038/ncomms6897
DO - 10.1038/ncomms6897
M3 - Journal article
C2 - 25631608
VL - 6
SP - 5897
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
ER -
ID: 135493847