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

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  • Jennifer Wessel

    (Fairbanks School of Public Health
    Indiana University School of Medicine)

  • Audrey Y Chu

    (Brigham and Women’s Hospital
    National Heart, Lung, and Blood Institute (NHLBI) Framingham Heart Study)

  • Sara M Willems

    (Genetic Epidemiology Unit, Erasmus University Medical Center
    MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus)

  • Shuai Wang

    (Boston University School of Public Health)

  • Hanieh Yaghootkar

    (Genetics of Complex Traits, University of Exeter Medical School, University of Exeter)

  • Jennifer A Brody

    (Cardiovascular Health Research Unit, University of Washington
    University of Washington)

  • Marco Dauriz

    (Massachusetts General Hospital
    Harvard Medical School
    Diabetes and Metabolism, University of Verona Medical School and Hospital Trust of Verona)

  • Marie-France Hivert

    (Harvard Pilgrim Health Care Institute, Harvard Medical School
    Université de Sherbrooke
    Diabetes Unit, Massachusetts General Hospital)

  • Sridharan Raghavan

    (Massachusetts General Hospital
    Harvard Medical School)

  • Leonard Lipovich

    (Center for Molecular Medicine and Genetics, Wayne State University
    Wayne State University School of Medicine)

  • Bertha Hidalgo

    (University of Alabama at Birmingham)

  • Keolu Fox

    (University of Washington
    University of Washington)

  • Jennifer E Huffman

    (National Heart, Lung, and Blood Institute (NHLBI) Framingham Heart Study
    MRC Human Genetics Unit, MRC IGMM, University of Edinburgh)

  • Ping An

    (Washington University School of Medicine)

  • Yingchang Lu

    (The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai
    The Genetics of Obesity and Related Metabolic Traits Program, The Icahn School of Medicine at Mount Sinai)

  • Laura J Rasmussen-Torvik

    (Northwestern University Feinberg School of Medicine)

  • Niels Grarup

    (The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen)

  • Margaret G Ehm

    (Quantitative Sciences, PCPS)

  • Li Li

    (Quantitative Sciences, PCPS)

  • Abigail S Baldridge

    (Northwestern University Feinberg School of Medicine)

  • Alena Stančáková

    (Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland)

  • Ravinder Abrol

    (Cedars-Sinai Medical Center
    Materials and Process Simulation Center, California Institute of Technology)

  • Céline Besse

    (CEA, Institut de Génomique, Centre National de Génotypage)

  • Anne Boland

    (CEA, Institut de Génomique, Centre National de Génotypage)

  • Jette Bork-Jensen

    (The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen)

  • Myriam Fornage

    (Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center)

  • Daniel F Freitag

    (The Wellcome Trust Sanger Institute
    Strangeways Research Laboratory, University of Cambridge)

  • Melissa E Garcia

    (Intramural Research Program, National Institute on Aging)

  • Xiuqing Guo

    (Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center)

  • Kazuo Hara

    (The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai
    The Genetics of Obesity and Related Metabolic Traits Program, The Icahn School of Medicine at Mount Sinai)

  • Aaron Isaacs

    (Genetic Epidemiology Unit, Erasmus University Medical Center)

  • Johanna Jakobsdottir

    (Icelandic Heart Association)

  • Leslie A Lange

    (University of North Carolina)

  • Jill C Layton

    (Indiana University, Fairbanks School of Public Health)

  • Man Li

    (Johns Hopkins University)

  • Jing Hua Zhao

    (MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus)

  • Karina Meidtner

    (German Institute of Human Nutrition Potsdam-Rehbrücke)

  • Alanna C Morrison

    (Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston)

  • Mike A Nalls

    (Laboratory of Neurogenetics, National Institute on Aging)

  • Marjolein J Peters

    (Erasmus University Medical Center
    The Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging (NGI-NCHA))

  • Maria Sabater-Lleal

    (Atherosclerosis Research Unit, Karolinska Institutet)

  • Claudia Schurmann

    (The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai
    The Genetics of Obesity and Related Metabolic Traits Program, The Icahn School of Medicine at Mount Sinai)

  • Angela Silveira

    (Atherosclerosis Research Unit, Karolinska Institutet)

  • Albert V Smith

    (Icelandic Heart Association
    University of Iceland)

  • Lorraine Southam

    (The Wellcome Trust Sanger Institute
    Wellcome Trust Centre for Human Genetics)

  • Marcus H Stoiber

    (Lawrence Berkeley National Laboratory)

  • Rona J Strawbridge

    (Atherosclerosis Research Unit, Karolinska Institutet)

  • Kent D Taylor

    (Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center)

  • Tibor V Varga

    (Genetic and Molecular Epidemiology Unit, Lund University, Skåne University Hospital)

  • Kristine H Allin

    (The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen)

  • Najaf Amin

    (Genetic Epidemiology Unit, Erasmus University Medical Center)

  • Jennifer L Aponte

    (Quantitative Sciences, PCPS)

  • Tin Aung

    (Singapore Eye Research Institute, Singapore National Eye Centre
    National University of Singapore and National University Health System)

  • Caterina Barbieri

    (San Raffaele Research Institute)

  • Nathan A Bihlmeyer

    (Predoctoral Training Program in Human Genetics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine
    McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine)

  • Michael Boehnke

    (University of Michigan)

  • Cristina Bombieri

    (Section of Biology and Genetics, University of Verona)

  • Donald W Bowden

    (Wake Forest School of Medicine)

  • Sean M Burns

    (Diabetes Unit, Massachusetts General Hospital)

  • Yuning Chen

    (Boston University School of Public Health)

  • Yii-DerI Chen

    (Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center)

  • Ching-Yu Cheng

    (Singapore Eye Research Institute, Singapore National Eye Centre
    National University of Singapore and National University Health System
    Saw Swee Hock School of Public Health, National University of Singapore and National University Health System
    Office of Clinical Sciences, Duke-NUS Graduate Medical School, National University of Singapore)

  • Adolfo Correa

    (University of Mississippi Medical Center)

  • Jacek Czajkowski

    (Washington University School of Medicine)

  • Abbas Dehghan

    (Erasmus University Medical Center)

  • Georg B Ehret

    (McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University
    Geneva University Hospital)

  • Gudny Eiriksdottir

    (Icelandic Heart Association)

  • Stefan A Escher

    (Genetic and Molecular Epidemiology Unit, Lund University, Skåne University Hospital)

  • Aliki-Eleni Farmaki

    (School of Health Science and Education, Harokopio University)

  • Mattias Frånberg

    (Atherosclerosis Research Unit, Karolinska Institutet
    SciLifeLab, Stockholm University)

  • Giovanni Gambaro

    (Columbus-Gemelli University Hospital, Catholic University)

  • Franco Giulianini

    (Brigham and Women’s Hospital)

  • William A Goddard

    (Materials and Process Simulation Center, California Institute of Technology)

  • Anuj Goel

    (The Wellcome Trust Centre for Human Genetics, University of Oxford)

  • Omri Gottesman

    (The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai)

  • Megan L Grove

    (Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston)

  • Stefan Gustafsson

    (Molecular Epidemiology and Science for Life Laboratory, Uppsala University)

  • Yang Hai

    (Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center)

  • Göran Hallmans

    (Umeå University)

  • Jiyoung Heo

    (Sangmyung University)

  • Per Hoffmann

    (Institute of Human Genetics, Life & Brain Center, University of Bonn
    Human Genomics Research Group
    Institute of Neuroscience and Medicine (INM-1) Genomic Imaging Research Center Juelich)

  • Mohammad K Ikram

    (Singapore Eye Research Institute, Singapore National Eye Centre
    Office of Clinical Sciences, Duke-NUS Graduate Medical School, National University of Singapore
    Memory Aging & Cognition Centre (MACC), National University Health System)

  • Richard A Jensen

    (Cardiovascular Health Research Unit, University of Washington
    University of Washington)

  • Marit E Jørgensen

    (Steno Diabetes Center)

  • Torben Jørgensen

    (Research Centre for Prevention and Health, Glostrup University Hospital
    Faculty of Medicine, University of Aalborg)

  • Maria Karaleftheri

    (Echinos Medical Centre)

  • Chiea C Khor

    (National University of Singapore and National University Health System
    Saw Swee Hock School of Public Health, National University of Singapore and National University Health System
    Genome Institute of Singapore)

  • Andrea Kirkpatrick

    (Materials and Process Simulation Center, California Institute of Technology)

  • Aldi T Kraja

    (Washington University School of Medicine)

  • Johanna Kuusisto

    (Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital)

  • Ethan M Lange

    (University of North Carolina
    University of North Carolina)

  • I T Lee

    (Taichung Veterans General Hospital
    School of Medicine, National Yang-Ming University)

  • Wen-Jane Lee

    (Taichung Veterans General Hospital)

  • Aaron Leong

    (Massachusetts General Hospital
    Harvard Medical School)

  • Jiemin Liao

    (Singapore Eye Research Institute, Singapore National Eye Centre
    National University of Singapore and National University Health System)

  • Chunyu Liu

    (National Heart, Lung, and Blood Institute (NHLBI) Framingham Heart Study)

  • Yongmei Liu

    (Wake Forest University)

  • Cecilia M Lindgren

    (Wellcome Trust Centre for Human Genetics, University of Oxford)

  • Allan Linneberg

    (Research Centre for Prevention and Health, Glostrup University Hospital
    Copenhagen University Hospital Glostrup
    Faculty of Health and Medical Sciences, University of Copenhagen)

  • Giovanni Malerba

    (Section of Biology and Genetics, University of Verona)

  • Vasiliki Mamakou

    (National and Kapodistrian University of Athens, Faculty of Medicine
    Dromokaiteio Psychiatric Hospital)

  • Eirini Marouli

    (School of Health Science and Education, Harokopio University)

  • Nisa M Maruthur

    (Johns Hopkins University School of Medicine
    Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University)

  • Angela Matchan

    (The Wellcome Trust Sanger Institute)

  • Roberta McKean-Cowdin

    (Keck School of Medicine of the University of Southern California)

  • Olga McLeod

    (Atherosclerosis Research Unit, Karolinska Institutet)

  • Ginger A Metcalf

    (Human Genome Sequencing Center, Baylor College of Medicine)

  • Karen L Mohlke

    (University of North Carolina)

  • Donna M Muzny

    (Human Genome Sequencing Center, Baylor College of Medicine)

  • Ioanna Ntalla

    (School of Health Science and Education, Harokopio University
    University of Leicester)

  • Nicholette D Palmer

    (Wake Forest School of Medicine
    Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine)

  • Dorota Pasko

    (Genetics of Complex Traits, University of Exeter Medical School, University of Exeter)

  • Andreas Peter

    (Metabolism, Pathobiochemistry and Clinical Chemistry and Institute of Diabetes Research and Metabolic Diseases, University of Tübingen
    German Center for Diabetes Research (DZD), Neuherberg)

  • Nigel W Rayner

    (The Wellcome Trust Sanger Institute
    Wellcome Trust Centre for Human Genetics
    The Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford)

  • Frida Renström

    (Genetic and Molecular Epidemiology Unit, Lund University, Skåne University Hospital)

  • Ken Rice

    (Cardiovascular Health Research Unit, University of Washington
    University of Washington)

  • Cinzia F Sala

    (San Raffaele Research Institute)

  • Bengt Sennblad

    (Atherosclerosis Research Unit, Karolinska Institutet
    Science for Life Laboratory, Karolinska Institutet)

  • Ioannis Serafetinidis

    (Gennimatas General Hospital)

  • Jennifer A Smith

    (School of Public Health, University of Michigan)

  • Nicole Soranzo

    (The Wellcome Trust Sanger Institute
    Department of Hematology)

  • Elizabeth K Speliotes

    (University of Michigan)

  • Eli A Stahl

    (The Icahn School of Medicine at Mount Sinai)

  • Kathleen Stirrups

    (The Wellcome Trust Sanger Institute
    William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London)

  • Nikos Tentolouris

    (Athens University Medical School, Laiko General Hospital)

  • Anastasia Thanopoulou

    (Diabetes Centre, National University of Athens, Hippokration General Hospital)

  • Mina Torres

    (Keck School of Medicine of the University of Southern California)

  • Michela Traglia

    (San Raffaele Research Institute)

  • Emmanouil Tsafantakis

    (Anogia Medical Centre)

  • Sundas Javad

    (MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus)

  • Lisa R Yanek

    (The GeneSTAR Research Program, The Johns Hopkins University School of Medicine)

  • Eleni Zengini

    (Dromokaiteio Psychiatric Hospital
    University of Sheffield)

  • Diane M Becker

    (The GeneSTAR Research Program, The Johns Hopkins University School of Medicine)

  • Joshua C Bis

    (Cardiovascular Health Research Unit, University of Washington
    University of Washington)

  • James B Brown

    (Lawrence Berkeley National Laboratory
    University of California at Berkeley)

  • L Adrienne Cupples

    (National Heart, Lung, and Blood Institute (NHLBI) Framingham Heart Study
    Boston University School of Public Health)

  • Torben Hansen

    (The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen
    Faculty of Health Science, University of Copenhagen)

  • Erik Ingelsson

    (Molecular Epidemiology and Science for Life Laboratory, Uppsala University
    Wellcome Trust Centre for Human Genetics, University of Oxford)

  • Andrew J Karter

    (Kaiser Permanente, Northern California Region)

  • Carlos Lorenzo

    (University of Texas Health Science Center)

  • Rasika A Mathias

    (The GeneSTAR Research Program, The Johns Hopkins University School of Medicine)

  • Jill M Norris

    (Colorado School of Public Health, University of Colorado Denver)

  • Gina M Peloso

    (Program in Medical and Population Genetics, Broad Institute
    Center for Human Genetic Research, Massachusetts General Hospital)

  • Wayne H.-H. Sheu

    (Taichung Veterans General Hospital
    School of Medicine, National Yang-Ming University
    College of Medicine, National Defense Medical Center)

  • Daniela Toniolo

    (San Raffaele Research Institute)

  • Dhananjay Vaidya

    (The GeneSTAR Research Program, The Johns Hopkins University School of Medicine)

  • Rohit Varma

    (Keck School of Medicine of the University of Southern California)

  • Lynne E Wagenknecht

    (Wake Forest School of Medicine)

  • Heiner Boeing

    (German Institute of Human Nutrition Potsdam Rehbrücke)

  • Erwin P Bottinger

    (The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai)

  • George Dedoussis

    (School of Health Science and Education, Harokopio University)

  • Panos Deloukas

    (William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London
    Wellcome Trust Sanger Institute
    Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University)

  • Ele Ferrannini

    (CNR Institute of Clinical Physiology)

  • Oscar H Franco

    (Erasmus University Medical Center)

  • Paul W Franks

    (Genetic and Molecular Epidemiology Unit, Lund University, Skåne University Hospital
    Harvard School of Public Health
    Umeå University)

  • Richard A Gibbs

    (Human Genome Sequencing Center, Baylor College of Medicine)

  • Vilmundur Gudnason

    (Icelandic Heart Association
    University of Iceland)

  • Anders Hamsten

    (Atherosclerosis Research Unit, Karolinska Institutet)

  • Tamara B Harris

    (Intramural Research Program, National Institute on Aging)

  • Andrew T Hattersley

    (Genetics of Diabetes, University of Exeter Medical School, University of Exeter)

  • Caroline Hayward

    (MRC Human Genetics Unit, MRC IGMM, University of Edinburgh)

  • Albert Hofman

    (Erasmus University Medical Center)

  • Jan-Håkan Jansson

    (Umeå University
    Research Unit)

  • Claudia Langenberg

    (MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus)

  • Lenore J Launer

    (Intramural Research Program, National Institute on Aging)

  • Daniel Levy

    (Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health
    Framingham Heart Study)

  • Ben A Oostra

    (Genetic Epidemiology Unit, Erasmus University Medical Center)

  • Christopher J O’Donnell

    (National Heart, Lung, and Blood Institute (NHLBI) Framingham Heart Study
    Harvard Medical School
    Massachusetts General Hospital and Harvard Medical School)

  • Stephen O’Rahilly

    (University of Cambridge Metabolic Research Laboratories, MRC Metabolic Diseases Unit and NIHR Cambridge Biomedical Research Centre, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke’s Hospital)

  • Sandosh Padmanabhan

    (Institute of Cardiovascular and Medical Sciences, University of Glasgow)

  • James S Pankow

    (School of Public Health, University of Minnesota)

  • Ozren Polasek

    (Faculty of Medicine, University of Split)

  • Michael A Province

    (Washington University School of Medicine)

  • Stephen S Rich

    (Center for Public Health Genomics, University of Virginia)

  • Paul M Ridker

    (Brigham and Women’s Hospital
    Brigham and Women’s Hospital and Harvard Medical School)

  • Igor Rudan

    (Centre for Population Health Sciences, Medical School, University of Edinburgh)

  • Matthias B Schulze

    (German Institute of Human Nutrition Potsdam-Rehbrücke
    German Center for Diabetes Research (DZD), Neuherberg)

  • Blair H Smith

    (Medical Research Institute, University of Dundee)

  • André G Uitterlinden

    (Erasmus University Medical Center
    Erasmus University Medical Center)

  • Mark Walker

    (Institute of Cellular Medicine, Newcastle University)

  • Hugh Watkins

    (The Wellcome Trust Centre for Human Genetics, University of Oxford)

  • Tien Y Wong

    (Singapore Eye Research Institute, Singapore National Eye Centre
    National University of Singapore and National University Health System
    Office of Clinical Sciences, Duke-NUS Graduate Medical School, National University of Singapore)

  • Eleftheria Zeggini

    (The Wellcome Trust Sanger Institute)

  • Markku Laakso

    (Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital)

  • Ingrid B Borecki

    (Washington University School of Medicine)

  • Daniel I Chasman

    (Brigham and Women’s Hospital
    Brigham and Women's Hospital and Harvard Medical School)

  • Oluf Pedersen

    (The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen)

  • Bruce M Psaty

    (Cardiovascular Health Research Unit, University of Washington
    University of Washington
    University of Washington
    University of Washington)

  • E Shyong Tai

    (Saw Swee Hock School of Public Health, National University of Singapore and National University Health System
    Yong Loo Lin School of Medicine, National University of Singapore)

  • Cornelia M van Duijn

    (Genetic Epidemiology Unit, Erasmus University Medical Center
    Center for Medical Systems Biology)

  • Nicholas J Wareham

    (MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus)

  • Dawn M Waterworth

    (Genetics, PCPS, GlaxoSmithKline)

  • Eric Boerwinkle

    (Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston
    Human Genome Sequencing Center, Baylor College of Medicine)

  • W H Linda Kao

    (Johns Hopkins University
    Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University
    Johns Hopkins University)

  • Jose C Florez

    (Harvard Medical School
    Diabetes Unit, Massachusetts General Hospital
    Program in Medical and Population Genetics, Broad Institute
    Center for Human Genetic Research, Massachusetts General Hospital)

  • Ruth J.F. Loos

    (The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai
    The Genetics of Obesity and Related Metabolic Traits Program, The Icahn School of Medicine at Mount Sinai
    The Mindich Child Health and Development Institute, The Icahn School of Medicine at Mount Sinai)

  • James G Wilson

    (University of Mississippi Medical Center)

  • Timothy M Frayling

    (Genetics of Complex Traits, University of Exeter Medical School, University of Exeter)

  • David S Siscovick

    (New York Academy of Medicine
    Cardiovascular Health Research Unit, University of Washington)

  • Josée Dupuis

    (National Heart, Lung, and Blood Institute (NHLBI) Framingham Heart Study
    Boston University School of Public Health)

  • Jerome I Rotter

    (Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center)

  • James B Meigs

    (Massachusetts General Hospital
    Harvard Medical School)

  • Robert A Scott

    (MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus)

  • Mark O Goodarzi

    (Cedars-Sinai Medical Center
    Diabetes and Metabolism, Cedars-Sinai Medical Center)

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.

Suggested Citation

  • 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 & Keol, 2015. "Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility," Nature Communications, Nature, vol. 6(1), pages 1-16, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms6897
    DOI: 10.1038/ncomms6897
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