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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-12

AUTHORS

Jennifer Wessel, Audrey Y Chu, Sara M Willems, Shuai Wang, Hanieh Yaghootkar, Jennifer A Brody, Marco Dauriz, Marie-France Hivert, Sridharan Raghavan, Leonard Lipovich, Bertha Hidalgo, Keolu Fox, Jennifer E Huffman, Ping An, Yingchang Lu, Laura J Rasmussen-Torvik, Niels Grarup, Margaret G Ehm, Li Li, Abigail S Baldridge, Alena Stančáková, Ravinder Abrol, Céline Besse, Anne Boland, Jette Bork-Jensen, Myriam Fornage, Daniel F Freitag, Melissa E Garcia, Xiuqing Guo, Kazuo Hara, Aaron Isaacs, Johanna Jakobsdottir, Leslie A Lange, Jill C Layton, Man Li, Jing Hua Zhao, Karina Meidtner, Alanna C Morrison, Mike A Nalls, Marjolein J Peters, Maria Sabater-Lleal, Claudia Schurmann, Angela Silveira, Albert V Smith, Lorraine Southam, Marcus H Stoiber, Rona J Strawbridge, Kent D Taylor, Tibor V Varga, Kristine H Allin, Najaf Amin, Jennifer L Aponte, Tin Aung, Caterina Barbieri, Nathan A Bihlmeyer, Michael Boehnke, Cristina Bombieri, Donald W Bowden, Sean M Burns, Yuning Chen, Yii-DerI Chen, Ching-Yu Cheng, Adolfo Correa, Jacek Czajkowski, Abbas Dehghan, Georg B Ehret, Gudny Eiriksdottir, Stefan A Escher, Aliki-Eleni Farmaki, Mattias Frånberg, Giovanni Gambaro, Franco Giulianini, William A Goddard, Anuj Goel, Omri Gottesman, Megan L Grove, Stefan Gustafsson, Yang Hai, Göran Hallmans, Jiyoung Heo, Per Hoffmann, Mohammad K Ikram, Richard A Jensen, Marit E Jørgensen, Torben Jørgensen, Maria Karaleftheri, Chiea C Khor, Andrea Kirkpatrick, Aldi T Kraja, Johanna Kuusisto, Ethan M Lange, I T Lee, Wen-Jane Lee, Aaron Leong, Jiemin Liao, Chunyu Liu, Yongmei Liu, Cecilia M Lindgren, Allan Linneberg, Giovanni Malerba, Vasiliki Mamakou, Eirini Marouli, Nisa M Maruthur, Angela Matchan, Roberta McKean-Cowdin, Olga McLeod, Ginger A Metcalf, Karen L Mohlke, Donna M Muzny, Ioanna Ntalla, Nicholette D Palmer, Dorota Pasko, Andreas Peter, Nigel W Rayner, Frida Renström, Ken Rice, Cinzia F Sala, Bengt Sennblad, Ioannis Serafetinidis, Jennifer A Smith, Nicole Soranzo, Elizabeth K Speliotes, Eli A Stahl, Kathleen Stirrups, Nikos Tentolouris, Anastasia Thanopoulou, Mina Torres, Michela Traglia, Emmanouil Tsafantakis, Sundas Javad, Lisa R Yanek, Eleni Zengini, Diane M Becker, Joshua C Bis, James B Brown, L Adrienne Cupples, Torben Hansen, Erik Ingelsson, Andrew J Karter, Carlos Lorenzo, Rasika A Mathias, Jill M Norris, Gina M Peloso, Wayne H.-H. Sheu, Daniela Toniolo, Dhananjay Vaidya, Rohit Varma, Lynne E Wagenknecht, Heiner Boeing, Erwin P Bottinger, George Dedoussis, Panos Deloukas, Ele Ferrannini, Oscar H Franco, Paul W Franks, Richard A Gibbs, Vilmundur Gudnason, Anders Hamsten, Tamara B Harris, Andrew T Hattersley, Caroline Hayward, Albert Hofman, Jan-Håkan Jansson, Claudia Langenberg, Lenore J Launer, Daniel Levy, Ben A Oostra, Christopher J O’Donnell, Stephen O’Rahilly, Sandosh Padmanabhan, James S Pankow, Ozren Polasek, Michael A Province, Stephen S Rich, Paul M Ridker, Igor Rudan, Matthias B Schulze, Blair H Smith, André G Uitterlinden, Mark Walker, Hugh Watkins, Tien Y Wong, Eleftheria Zeggini, The EPIC-InterAct Consortium, Stephen J Sharp, Nita G Forouhi, Nicola D Kerrison, Debora ME Lucarelli, Matt Sims, Inês Barroso, Mark I McCarthy, Larraitz Arriola, Beverley Balkau, Aurelio Barricarte, Carlos Gonzalez, Sara Grioni, Rudolf Kaaks, Timothy J Key, Carmen Navarro, Peter M Nilsson, Kim Overvad, Domenico Palli, Salvatore Panico, J. Ramón Quirós, Olov Rolandsson, Carlotta Sacerdote, María–José Sánchez, Nadia Slimani, Anne Tjonneland, Rosario Tumino, Daphne L van der A, Yvonne T van der Schouw, Elio Riboli, Markku Laakso, Ingrid B Borecki, Daniel I Chasman, Oluf Pedersen, Bruce M Psaty, E Shyong Tai, Cornelia M van Duijn, Nicholas J Wareham, Dawn M Waterworth, Eric Boerwinkle, W H Linda Kao, Jose C Florez, Ruth J.F. Loos, James G Wilson, Timothy M Frayling, David S Siscovick, Josée Dupuis, Jerome I Rotter, James B Meigs, Robert A Scott, Mark O Goodarzi

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. More... »

PAGES

5897

References to SciGraph publications

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  • Journal

    TITLE

    Nature Communications

    ISSUE

    1

    VOLUME

    6

    Author Affiliations

  • Indiana University – Purdue University Indianapolis
  • National Heart Lung and Blood Institute
  • Institute of Metabolic Science
  • Boston University
  • University of Exeter
  • University of Washington
  • University of Verona
  • Massachusetts General Hospital
  • Harvard University
  • Wayne State University
  • University of Alabama at Birmingham
  • University of Edinburgh
  • Washington University in St. Louis
  • Icahn School of Medicine at Mount Sinai
  • Northwestern University
  • University of Copenhagen
  • GlaxoSmithKline (United States)
  • University of Eastern Finland
  • California Institute of Technology
  • The University of Texas Health Science Center at Houston
  • University of Cambridge
  • National Institute on Aging
  • Harbor–UCLA Medical Center
  • Erasmus University Medical Center
  • Icelandic Heart Association
  • University of North Carolina at Chapel Hill
  • Johns Hopkins University
  • German Institute of Human Nutrition
  • Wageningen University & Research
  • Karolinska Institute
  • University of Iceland
  • Wellcome Centre for Human Genetics
  • Lawrence Berkeley National Laboratory
  • Singapore National Eye Center
  • University of Michigan–Ann Arbor
  • Wake Forest University
  • National University of Singapore
  • University of Mississippi Medical Center
  • Harokopio University
  • Stockholm University
  • Catholic University of the Sacred Heart
  • Brigham and Women's Hospital
  • Uppsala University
  • Umeå University
  • Sangmyung University
  • Forschungszentrum Jülich
  • National University Health System
  • Steno Diabetes Center
  • Aalborg University
  • Genome Institute of Singapore
  • University of North Carolina System
  • National Yang Ming University
  • Taichung Veterans General Hospital
  • National and Kapodistrian University of Athens
  • Wellcome Sanger Institute
  • University of Southern California
  • Baylor College of Medicine
  • University of Leicester
  • German Center for Diabetes Research
  • University of Oxford
  • General Hospital of Athens G. Genimatas
  • Queen Mary University of London
  • University of Sheffield
  • University of California, Berkeley
  • Kaiser Permanente
  • The University of Texas Health Science Center at San Antonio
  • University of Colorado Anschutz Medical Campus
  • National Defense Medical Center
  • King Abdulaziz University
  • Istituto di Fisiologia Clinica
  • University of Glasgow
  • University of Minnesota
  • University of Split
  • University of Virginia
  • University of Dundee
  • Newcastle University
  • NIHR Oxford Musculoskeletal Biomedical Research Unit
  • Instituto de Salud Carlos III
  • University of Paris-Sud
  • Instituto de Salud Pública de Navarra
  • Institut Català d'Oncologia
  • German Cancer Research Center
  • University of Murcia
  • Aalborg Hospital
  • Istituto per lo Studio e la Prevenzione Oncologica
  • University of Naples Federico II
  • Human Genetics Foundation
  • Andalusian School of Public Health
  • International Agency For Research On Cancer
  • Danish Cancer Society
  • National Institute for Public Health and the Environment
  • University Medical Center Utrecht
  • Imperial College London
  • Group Health Cooperative
  • Cedars-Sinai Medical Center
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ncomms6897

    DOI

    http://dx.doi.org/10.1038/ncomms6897

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1029757015

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/25631608


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