Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility
dc.contributor.author | Wessel, Jennifer | |
dc.contributor.author | Chu, Audrey Y. | |
dc.contributor.author | Willems, Sara M. | |
dc.contributor.author | Wang, Shuai | |
dc.contributor.author | Yaghootkar, Hanieh | |
dc.contributor.author | Brody, Jennifer A. | |
dc.contributor.author | Dauriz, Marco | |
dc.contributor.author | Hivert, Marie-France | |
dc.contributor.author | Raghavan, Sridharan | |
dc.contributor.author | Lipovich, Leonard | |
dc.contributor.author | Hidalgo, Bertha | |
dc.contributor.author | Fox, Keolu | |
dc.contributor.author | Huffman, Jennifer E. | |
dc.contributor.author | An, Ping | |
dc.contributor.author | Lu, Yingchang | |
dc.contributor.author | Rasmussen-Torvik, Laura J. | |
dc.contributor.author | Grarup, Niels | |
dc.contributor.author | Ehm, Margaret G. | |
dc.contributor.author | Li, Li | |
dc.contributor.author | Baldridge, Abigail S. | |
dc.contributor.author | Stančáková, Alena | |
dc.contributor.author | Abrol, Ravinder | |
dc.contributor.author | Besse, Céline | |
dc.contributor.author | Boland, Anne | |
dc.contributor.author | Bork-Jensen, Jette | |
dc.contributor.author | Fornage, Myriam | |
dc.contributor.author | Freitag, Daniel F. | |
dc.contributor.author | Garcia, Melissa E. | |
dc.contributor.author | Guo, Xiuqing | |
dc.contributor.author | Hara, Kazuo | |
dc.contributor.author | Isaacs, Aaron | |
dc.contributor.author | Jakobsdottir, Johanna | |
dc.contributor.author | Lange, Leslie A. | |
dc.contributor.author | Layton, Jill C. | |
dc.contributor.author | Li, Man | |
dc.contributor.author | Hua Zhao, Jing | |
dc.contributor.author | Meidtner, Karina | |
dc.contributor.author | Morrison, Alanna C. | |
dc.contributor.author | Nalls, Mike A. | |
dc.contributor.author | Peters, Marjolein J. | |
dc.contributor.author | Sabater-Lleal, Maria | |
dc.contributor.author | Schurmann, Claudia | |
dc.contributor.author | Silveira, Angela | |
dc.contributor.author | Smith, Albert V. | |
dc.contributor.author | Southam, Lorraine | |
dc.contributor.author | Stoiber, Marcus H. | |
dc.contributor.author | Strawbridge, Rona J. | |
dc.contributor.author | Taylor, Kent D. | |
dc.contributor.author | Varga, Tibor V. | |
dc.contributor.author | Allin, Kristine H. | |
dc.contributor.author | Amin, Najaf | |
dc.contributor.author | Aponte, Jennifer L. | |
dc.contributor.author | Aung, Tin | |
dc.contributor.author | Barbieri, Caterina | |
dc.contributor.author | Bihlmeyer, Nathan A. | |
dc.contributor.author | Boehnke, Michael | |
dc.contributor.author | Bombieri, Cristina | |
dc.contributor.author | Bowden, Donald W. | |
dc.contributor.author | Burns, Sean M. | |
dc.contributor.author | Chen, Yuning | |
dc.contributor.author | Chen, Yii-DerI | |
dc.contributor.author | Cheng, Ching-Yu | |
dc.contributor.author | Correa, Adolfo | |
dc.contributor.author | Czajkowski, Jacek | |
dc.contributor.author | Dehghan, Abbas | |
dc.contributor.author | Ehret, Georg B. | |
dc.contributor.author | Eiriksdottir, Gudny | |
dc.contributor.author | Escher, Stefan A. | |
dc.contributor.author | Farmaki, Aliki-Eleni | |
dc.contributor.author | Frånberg, Mattias | |
dc.contributor.author | Gambaro, Giovanni | |
dc.contributor.author | Giulianini, Franco | |
dc.contributor.author | Goddard, William A. | |
dc.contributor.author | Goel, Anuj | |
dc.contributor.author | Gottesman, Omri | |
dc.contributor.author | Grove, Megan L. | |
dc.contributor.author | Gustafsson, Stefan | |
dc.contributor.author | Hai, Yang | |
dc.contributor.author | Hallmans, Göran | |
dc.contributor.author | Heo, Jiyoung | |
dc.contributor.author | Hoffmann, Per | |
dc.contributor.author | Ikram, Mohammad K. | |
dc.contributor.author | Jensen, Richard A. | |
dc.contributor.author | Jørgensen, Marit E. | |
dc.contributor.author | Jørgensen, Torben | |
dc.contributor.author | Karaleftheri, Maria | |
dc.contributor.author | Khor, Chiea C. | |
dc.contributor.author | Kirkpatrick, Andrea | |
dc.contributor.author | Kraja, Aldi T. | |
dc.contributor.author | Kuusisto, Johanna | |
dc.contributor.author | Lange, Ethan M. | |
dc.contributor.author | Lee, I. T. | |
dc.contributor.author | Lee, Wen-Jane | |
dc.contributor.author | Leong, Aaron | |
dc.contributor.author | Liao, Jiemin | |
dc.contributor.author | Liu, Chunyu | |
dc.contributor.author | Liu, Yongmei | |
dc.contributor.author | Lindgren, Cecilia M. | |
dc.contributor.author | Linneberg, Allan | |
dc.contributor.author | Malerba, Giovanni | |
dc.contributor.author | Mamakou, Vasiliki | |
dc.contributor.author | Marouli, Eirini | |
dc.contributor.author | Maruthur, Nisa M. | |
dc.contributor.author | Matchan, Angela | |
dc.contributor.author | McKean-Cowdin, Roberta | |
dc.contributor.author | McLeod, Olga | |
dc.contributor.author | Metcalf, Ginger A. | |
dc.contributor.author | Mohlke, Karen L. | |
dc.contributor.author | Muzny, Donna M. | |
dc.contributor.author | Ntalla, Ioanna | |
dc.contributor.author | Palmer, Nicholette D. | |
dc.contributor.author | Pasko, Dorota | |
dc.contributor.author | Peter, Andreas | |
dc.contributor.author | Rayner, Nigel W. | |
dc.contributor.author | Renström, Frida | |
dc.contributor.author | Rice, Ken | |
dc.contributor.author | Sala, Cinzia F. | |
dc.contributor.author | Sennblad, Bengt | |
dc.contributor.author | Serafetinidis, Ioannis | |
dc.contributor.author | Smith, Jennifer A. | |
dc.contributor.author | Soranzo, Nicole | |
dc.contributor.author | Speliotes, Elizabeth K. | |
dc.contributor.author | Stahl, Eli A. | |
dc.contributor.author | Stirrups, Kathleen | |
dc.contributor.author | Tentolouris, Nikos | |
dc.contributor.author | Thanopoulou, Anastasia | |
dc.contributor.author | Torres, Mina | |
dc.contributor.author | Traglia, Michela | |
dc.contributor.author | Tsafantakis, Emmanouil | |
dc.contributor.author | Javad, Sundas | |
dc.contributor.author | Yanek, Lisa R. | |
dc.contributor.author | Zengini, Eleni | |
dc.contributor.author | Becker, Diane M. | |
dc.contributor.author | Bis, Joshua C. | |
dc.contributor.author | Brown, James B. | |
dc.contributor.author | Adrienne Cupples, L. | |
dc.contributor.author | Hansen, Torben | |
dc.contributor.author | Ingelsson, Erik | |
dc.contributor.author | Karter, Andrew J. | |
dc.contributor.author | Lorenzo, Carlos | |
dc.contributor.author | Mathias, Rasika A. | |
dc.contributor.author | Norris, Jill M. | |
dc.contributor.author | Peloso, Gina M. | |
dc.contributor.author | Sheu, Wayne H.-H. | |
dc.contributor.author | Toniolo, Daniela | |
dc.contributor.author | Vaidya, Dhananjay | |
dc.contributor.author | Varma, Rohit | |
dc.contributor.author | Wagenknecht, Lynne E. | |
dc.contributor.author | Boeing, Heiner | |
dc.contributor.author | Bottinger, Erwin P. | |
dc.contributor.author | Dedoussis, George | |
dc.contributor.author | Deloukas, Panos | |
dc.contributor.author | Ferrannini, Ele | |
dc.contributor.author | Franco, Oscar H. | |
dc.contributor.author | Franks, Paul W. | |
dc.contributor.author | Gibbs, Richard A. | |
dc.contributor.author | Gudnason, Vilmundur | |
dc.contributor.author | Hamsten, Anders | |
dc.contributor.author | Harris, Tamara B. | |
dc.contributor.author | Hattersley, Andrew T. | |
dc.contributor.author | Hayward, Caroline | |
dc.contributor.author | Hofman, Albert | |
dc.contributor.author | Jansson, Jan-Håkan | |
dc.contributor.author | Langenberg, Claudia | |
dc.contributor.author | Launer, Lenore J. | |
dc.contributor.author | Levy, Daniel | |
dc.contributor.author | Oostra, Ben A. | |
dc.contributor.author | O'Donnell, Christopher J. | |
dc.contributor.author | O'Rahilly, Stephen | |
dc.contributor.author | Padmanabhan, Sandosh | |
dc.contributor.author | Pankow, James S. | |
dc.contributor.author | Polasek, Ozren | |
dc.contributor.author | Province, Michael A. | |
dc.contributor.author | Rich, Stephen S. | |
dc.contributor.author | Ridker, Paul M. | |
dc.contributor.author | Rudan, Igor | |
dc.contributor.author | Schulze, Matthias B. | |
dc.contributor.author | Smith, Blair H. | |
dc.contributor.author | Uitterlinden, André G. | |
dc.contributor.author | Walker, Mark | |
dc.contributor.author | Watkins, Hugh | |
dc.contributor.author | Wong, Tien Y. | |
dc.contributor.author | Zeggini, Eleftheria | |
dc.contributor.author | Laakso, Markku | |
dc.contributor.author | Borecki, Ingrid B. | |
dc.contributor.author | Chasman, Daniel I. | |
dc.contributor.author | Pedersen, Oluf | |
dc.contributor.author | Psaty, Bruce M. | |
dc.contributor.author | Shyong Tai, E. | |
dc.contributor.author | van Duijn, Cornelia M. | |
dc.contributor.author | Wareham, Nicholas J. | |
dc.contributor.author | Waterworth, Dawn M. | |
dc.contributor.author | Boerwinkle, Eric | |
dc.contributor.author | Linda Kao, W. H. | |
dc.contributor.author | Florez, Jose C. | |
dc.contributor.author | Loos, Ruth J. F. | |
dc.contributor.author | Wilson, James G. | |
dc.contributor.author | Frayling, Timothy M. | |
dc.contributor.author | Siscovick, David S. | |
dc.contributor.author | Dupuis, Josée | |
dc.contributor.author | Rotter, Jerome I. | |
dc.contributor.author | Meigs, James B. | |
dc.contributor.author | Scott, Robert A. | |
dc.contributor.author | Goodarzi, Mark O. | |
dc.contributor.department | Department of Epidemiology, Richard M. Fairbanks School of Public Health | en_US |
dc.date.accessioned | 2016-03-18T20:18:14Z | |
dc.date.available | 2016-03-18T20:18:14Z | |
dc.date.issued | 2015-01-29 | |
dc.description.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. | en_US |
dc.eprint.version | Final published version | en_US |
dc.identifier.citation | Wessel, J., Chu, A. Y., Willems, S. M., Wang, S., Yaghootkar, H., Brody, J. A., … Goodarzi, M. O. (2015). Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility. Nature Communications, 6, 5897. http://doi.org/10.1038/ncomms6897 | en_US |
dc.identifier.issn | 2041-1723 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/8945 | |
dc.language.iso | en_US | en_US |
dc.publisher | Nature Publishing Group | en_US |
dc.relation.isversionof | 10.1038/ncomms6897 | en_US |
dc.relation.journal | Nature Communications | en_US |
dc.rights | Attribution 3.0 United States | |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/us/ | |
dc.source | Publisher | en_US |
dc.subject | Blood Glucose | en_US |
dc.subject | metabolism | en_US |
dc.subject | Diabetes Mellitus, Type 2 | en_US |
dc.subject | genetics | en_US |
dc.subject | Exome | en_US |
dc.subject | Fasting | en_US |
dc.subject | blood | en_US |
dc.subject | Genetic Predisposition to Disease | en_US |
dc.subject | Mutation Rate | en_US |
dc.subject | Oligonucleotide Array Sequence Analysis | en_US |
dc.title | Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility | en_US |
dc.type | Article | en_US |
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