Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility
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Author
Wessel, Jennifer
Chu, Audrey Y
Willems, Sara M
Wang, Shuai
Yaghootkar, Hanieh
Brody, Jennifer A
Dauriz, Marco
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
Stoiber, Marcus H
Strawbridge, Rona J
Taylor, Kent D
Varga, Tibor V
Allin, Kristine H
Amin, Najaf
Aponte, Jennifer L
Aung, Tin
Barbieri, Caterina
Bihlmeyer, Nathan A
Boehnke, Michael
Bombieri, Cristina
Bowden, Donald W
Chen, Yuning
Chen, Yii-DerI
Cheng, Ching-Yu
Correa, Adolfo
Czajkowski, Jacek
Dehghan, Abbas
Ehret, Georg B
Eiriksdottir, Gudny
Escher, Stefan A
Farmaki, Aliki-Eleni
Frånberg, Mattias
Gambaro, Giovanni
Giulianini, Franco
Goddard, William A
Goel, Anuj
Gottesman, Omri
Grove, Megan L
Gustafsson, Stefan
Hai, Yang
Hallmans, Göran
Heo, Jiyoung
Hoffmann, Per
Ikram, Mohammad K
Jensen, Richard A
Jørgensen, Marit E
Jørgensen, Torben
Karaleftheri, Maria
Khor, Chiea C
Kirkpatrick, Andrea
Kraja, Aldi T
Kuusisto, Johanna
Lange, Ethan M
Lee, I T
Lee, Wen-Jane
Liao, Jiemin
Liu, Chunyu
Liu, Yongmei
Lindgren, Cecilia M
Linneberg, Allan
Malerba, Giovanni
Mamakou, Vasiliki
Marouli, Eirini
Maruthur, Nisa M
Matchan, Angela
McKean-Cowdin, Roberta
McLeod, Olga
Metcalf, Ginger A
Mohlke, Karen L
Muzny, Donna M
Ntalla, Ioanna
Palmer, Nicholette D
Pasko, Dorota
Peter, Andreas
Rayner, Nigel W
Renström, Frida
Rice, Ken
Sala, Cinzia F
Sennblad, Bengt
Serafetinidis, Ioannis
Smith, Jennifer A
Soranzo, Nicole
Speliotes, Elizabeth K
Stahl, Eli A
Stirrups, Kathleen
Tentolouris, Nikos
Thanopoulou, Anastasia
Torres, Mina
Traglia, Michela
Tsafantakis, Emmanouil
Javad, Sundas
Yanek, Lisa R
Zengini, Eleni
Becker, Diane M
Bis, Joshua C
Brown, James B
Adrienne Cupples, L
Hansen, Torben
Ingelsson, Erik
Karter, Andrew J
Lorenzo, Carlos
Mathias, Rasika A
Norris, Jill M
Sheu, Wayne H.-H.
Toniolo, Daniela
Vaidya, Dhananjay
Varma, Rohit
Wagenknecht, Lynne E
Boeing, Heiner
Bottinger, Erwin P
Dedoussis, George
Deloukas, Panos
Ferrannini, Ele
Franco, Oscar H
Franks, Paul W
Gibbs, Richard A
Gudnason, Vilmundur
Hamsten, Anders
Harris, Tamara B
Hattersley, Andrew T
Hayward, Caroline
Hofman, Albert
Jansson, Jan-Håkan
Langenberg, Claudia
Launer, Lenore J
Levy, Daniel
Oostra, Ben A
O'Rahilly, Stephen
Padmanabhan, Sandosh
Pankow, James S
Polasek, Ozren
Province, Michael A
Rich, Stephen S
Rudan, Igor
Schulze, Matthias B
Smith, Blair H
Uitterlinden, André G
Walker, Mark
Watkins, Hugh
Wong, Tien Y
Zeggini, Eleftheria
Sharp, Stephen J
Forouhi, Nita G
Kerrison, Nicola D
Lucarelli, Debora ME
Sims, Matt
Barroso, Inês
McCarthy, Mark I
Arriola, Larraitz
Balkau, Beverley
Barricarte, Aurelio
Gonzalez, Carlos
Grioni, Sara
Kaaks, Rudolf
Key, Timothy J
Navarro, Carmen
Nilsson, Peter M
Overvad, Kim
Palli, Domenico
Panico, Salvatore
Quirós, J. Ramón
Rolandsson, Olov
Sacerdote, Carlotta
Sánchez, María–José
Slimani, Nadia
Tjonneland, Anne
Tumino, Rosario
van der A, Daphne L
van der Schouw, Yvonne T
Riboli, Elio
Laakso, Markku
Borecki, Ingrid B
Pedersen, Oluf
Psaty, Bruce M
Shyong Tai, E
van Duijn, Cornelia M
Wareham, Nicholas J
Waterworth, Dawn M
Boerwinkle, Eric
Linda Kao, W H
Loos, Ruth J.F.
Wilson, James G
Frayling, Timothy M
Siscovick, David S
Dupuis, Josée
Rotter, Jerome I
Scott, Robert A
Goodarzi, Mark O
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https://doi.org/10.1038/ncomms6897Metadata
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Wessel, J., A. Y. Chu, S. M. Willems, S. Wang, H. Yaghootkar, J. A. Brody, M. Dauriz, et al. 2015. “Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility.” Nature Communications 6 (1): 5897. doi:10.1038/ncomms6897. http://dx.doi.org/10.1038/ncomms6897.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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4311266/pdf/Terms of Use
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