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Genome-Wide Association Analysis Identifies Variants Associated with Nonalcoholic Fatty Liver Disease That Have Distinct Effects on Metabolic Traits

  • Elizabeth K. Speliotes equal contributor mail,

    equal contributor Contributed equally to this work with: Elizabeth K. Speliotes, Laura M. Yerges-Armstrong, Jun Wu, Ruben Hernaez, Lauren J. Kim, Albert V. Smith, W. H. Linda Kao, Joel N. Hirschhorn, Ingrid B. Borecki

    espeliot@med.umich.edu (EKS); iborecki@wustl.edu (IBB)

    Affiliations: Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan, United States of America, Center for Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, United States of America, Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, United States of America, Broad Institute, Cambridge, Massachusetts, United States of America

    X
  • Laura M. Yerges-Armstrong equal contributor,

    equal contributor Contributed equally to this work with: Elizabeth K. Speliotes, Laura M. Yerges-Armstrong, Jun Wu, Ruben Hernaez, Lauren J. Kim, Albert V. Smith, W. H. Linda Kao, Joel N. Hirschhorn, Ingrid B. Borecki

    Affiliation: Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, United States of America

    X
  • Jun Wu equal contributor,

    equal contributor Contributed equally to this work with: Elizabeth K. Speliotes, Laura M. Yerges-Armstrong, Jun Wu, Ruben Hernaez, Lauren J. Kim, Albert V. Smith, W. H. Linda Kao, Joel N. Hirschhorn, Ingrid B. Borecki

    Affiliation: Division of Statistical Genomics, Department of Genetics, Washington University, Saint Louis, Missouri, United States of America

    X
  • Ruben Hernaez equal contributor,

    equal contributor Contributed equally to this work with: Elizabeth K. Speliotes, Laura M. Yerges-Armstrong, Jun Wu, Ruben Hernaez, Lauren J. Kim, Albert V. Smith, W. H. Linda Kao, Joel N. Hirschhorn, Ingrid B. Borecki

    Affiliations: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America, Division of General Internal Medicine, The Johns Hopkins Hospital, Baltimore, Maryland, United States of America, Department of Internal Medicine, Washington Hospital Center, Washington D.C., United States of America

    X
  • Lauren J. Kim equal contributor,

    equal contributor Contributed equally to this work with: Elizabeth K. Speliotes, Laura M. Yerges-Armstrong, Jun Wu, Ruben Hernaez, Lauren J. Kim, Albert V. Smith, W. H. Linda Kao, Joel N. Hirschhorn, Ingrid B. Borecki

    Affiliation: Laboratory of Epidemiology, Demography, and Biometry, Intramural Research Program, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America

    X
  • Cameron D. Palmer,

    Affiliation: Divisions of Endocrinology and Genetics and Program in Genomics, Children's Hospital, Boston, Massachusetts, United States of America

    X
  • Vilmundur Gudnason,

    Affiliations: Icelandic Heart Association, Kopavogur, Iceland, University of Iceland, Reykjavik, Iceland

    X
  • Gudny Eiriksdottir,

    Affiliation: Icelandic Heart Association, Kopavogur, Iceland

    X
  • Melissa E. Garcia,

    Affiliation: Laboratory of Epidemiology, Demography, and Biometry, Intramural Research Program, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America

    X
  • Lenore J. Launer,

    Affiliation: Laboratory of Epidemiology, Demography, and Biometry, Intramural Research Program, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America

    X
  • Michael A. Nalls,

    Affiliation: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America

    X
  • Jeanne M. Clark,

    Affiliations: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America, Division of General Internal Medicine, The Johns Hopkins Hospital, Baltimore, Maryland, United States of America, Welch Center for Prevention, Epidemiology, and Clinical Research, Baltimore, Maryland, United States of America

    X
  • Braxton D. Mitchell,

    Affiliation: Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, United States of America

    X
  • Alan R. Shuldiner,

    Affiliations: Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, United States of America, Geriatric Research and Education Clinical Center (GRECC), Veterans Administration Medical Center, Baltimore, Maryland, United States of America

    X
  • Johannah L. Butler,

    Affiliations: Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan, United States of America, Center for Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, United States of America, Divisions of Endocrinology and Genetics and Program in Genomics, Children's Hospital, Boston, Massachusetts, United States of America

    X
  • Marta Tomas,

    Affiliations: Cardiovascular Epidemiology and Genetics, Institut Municipal d'Investigació Mèdica, Barcelona, Spain, CIBER Epidemiología y Salud Pública, Barcelona, Spain

    X
  • Udo Hoffmann,

    Affiliations: Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts, United States of America, Division of Cardiology, Massachusetts General Hospital, Boston, Massachusetts, United States of America

    X
  • Shih-Jen Hwang,

    Affiliation: Framingham Heart Study, National Heart, Lung, and Blood Institute (NHLBI), Framingham, Massachusetts, United States of America

    X
  • Joseph M. Massaro,

    Affiliations: Framingham Heart Study, National Heart, Lung, and Blood Institute (NHLBI), Framingham, Massachusetts, United States of America, Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, United States of America

    X
  • Christopher J. O'Donnell,

    Affiliations: Division of Cardiology, Massachusetts General Hospital, Boston, Massachusetts, United States of America, Framingham Heart Study, National Heart, Lung, and Blood Institute (NHLBI), Framingham, Massachusetts, United States of America, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland, United States of America

    X
  • Dushyant V. Sahani,

    Affiliation: Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts, United States of America

    X
  • Veikko Salomaa,

    Affiliation: Chronic Disease Epidemiology Unit, Department of Health Promotion and Chronic Disease Prevention, National Public Health Institute, Helsinki, Finland

    X
  • Eric E. Schadt,

    Affiliation: Pacific Biosciences, Menlo Park, California, United States of America

    X
  • Stephen M. Schwartz,

    Affiliations: Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology, University of Washington, Seattle, Washington, United States of America, Department of Epidemiology, University of Washington, Seattle, Washington, United States of America

    X
  • David S. Siscovick,

    Affiliation: Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology, University of Washington, Seattle, Washington, United States of America

    X
  • NASH CRN ,

    For membership information, please see Acknowledgments.

    X
  • GIANT Consortium ,

    For membership information, please see Acknowledgments.

    X
  • MAGIC Investigators ,

    For membership information, please see Acknowledgments.

    X
  • Benjamin F. Voight,

    Affiliation: Broad Institute, Cambridge, Massachusetts, United States of America

    X
  • J. Jeffrey Carr,

    Affiliation: Departments of Radiologic Sciences, Internal Medicine-Cardiology, and Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States of America

    X
  • Mary F. Feitosa,

    Affiliation: Division of Statistical Genomics, Department of Genetics, Washington University, Saint Louis, Missouri, United States of America

    X
  • Tamara B. Harris,

    Affiliation: Laboratory of Epidemiology, Demography, and Biometry, Intramural Research Program, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America

    X
  • Caroline S. Fox,

    Affiliations: Framingham Heart Study, National Heart, Lung, and Blood Institute (NHLBI), Framingham, Massachusetts, United States of America, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland, United States of America

    X
  • Albert V. Smith equal contributor,

    equal contributor Contributed equally to this work with: Elizabeth K. Speliotes, Laura M. Yerges-Armstrong, Jun Wu, Ruben Hernaez, Lauren J. Kim, Albert V. Smith, W. H. Linda Kao, Joel N. Hirschhorn, Ingrid B. Borecki

    Affiliation: Icelandic Heart Association, Kopavogur, Iceland

    X
  • W. H. Linda Kao equal contributor,

    equal contributor Contributed equally to this work with: Elizabeth K. Speliotes, Laura M. Yerges-Armstrong, Jun Wu, Ruben Hernaez, Lauren J. Kim, Albert V. Smith, W. H. Linda Kao, Joel N. Hirschhorn, Ingrid B. Borecki

    Affiliations: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America, Welch Center for Prevention, Epidemiology, and Clinical Research, Baltimore, Maryland, United States of America

    X
  • Joel N. Hirschhorn equal contributor,

    equal contributor Contributed equally to this work with: Elizabeth K. Speliotes, Laura M. Yerges-Armstrong, Jun Wu, Ruben Hernaez, Lauren J. Kim, Albert V. Smith, W. H. Linda Kao, Joel N. Hirschhorn, Ingrid B. Borecki

    Affiliations: Broad Institute, Cambridge, Massachusetts, United States of America, Divisions of Endocrinology and Genetics and Program in Genomics, Children's Hospital, Boston, Massachusetts, United States of America, Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America

    X
  • Ingrid B. Borecki equal contributor mail,

    equal contributor Contributed equally to this work with: Elizabeth K. Speliotes, Laura M. Yerges-Armstrong, Jun Wu, Ruben Hernaez, Lauren J. Kim, Albert V. Smith, W. H. Linda Kao, Joel N. Hirschhorn, Ingrid B. Borecki

    espeliot@med.umich.edu (EKS); iborecki@wustl.edu (IBB)

    Affiliation: Division of Statistical Genomics, Department of Genetics, Washington University, Saint Louis, Missouri, United States of America

    X
  • GOLD Consortium

    For membership information, please see Acknowledgments.

    X
  • Published: March 10, 2011
  • DOI: 10.1371/journal.pgen.1001324

About the Authors

Elizabeth K. Speliotes, Johannah L. Butler
Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan, United States of America
Elizabeth K. Speliotes, Johannah L. Butler
Center for Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, United States of America
Elizabeth K. Speliotes
Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, United States of America
Elizabeth K. Speliotes, Benjamin F. Voight, Joel N. Hirschhorn
Broad Institute, Cambridge, Massachusetts, United States of America
Laura M. Yerges-Armstrong, Braxton D. Mitchell, Alan R. Shuldiner
Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, United States of America
Jun Wu, Mary F. Feitosa, Ingrid B. Borecki
Division of Statistical Genomics, Department of Genetics, Washington University, Saint Louis, Missouri, United States of America
Ruben Hernaez, Jeanne M. Clark, W. H. Linda Kao
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America
Ruben Hernaez, Jeanne M. Clark
Division of General Internal Medicine, The Johns Hopkins Hospital, Baltimore, Maryland, United States of America
Ruben Hernaez
Department of Internal Medicine, Washington Hospital Center, Washington D.C., United States of America
Lauren J. Kim, Melissa E. Garcia, Lenore J. Launer, Tamara B. Harris
Laboratory of Epidemiology, Demography, and Biometry, Intramural Research Program, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America
Cameron D. Palmer, Johannah L. Butler, Joel N. Hirschhorn
Divisions of Endocrinology and Genetics and Program in Genomics, Children's Hospital, Boston, Massachusetts, United States of America
Vilmundur Gudnason, Gudny Eiriksdottir, Albert V. Smith
Icelandic Heart Association, Kopavogur, Iceland
Vilmundur Gudnason
University of Iceland, Reykjavik, Iceland
Michael A. Nalls
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America
Jeanne M. Clark, W. H. Linda Kao
Welch Center for Prevention, Epidemiology, and Clinical Research, Baltimore, Maryland, United States of America
Alan R. Shuldiner
Geriatric Research and Education Clinical Center (GRECC), Veterans Administration Medical Center, Baltimore, Maryland, United States of America
Marta Tomas
Cardiovascular Epidemiology and Genetics, Institut Municipal d'Investigació Mèdica, Barcelona, Spain
Marta Tomas
CIBER Epidemiología y Salud Pública, Barcelona, Spain
Udo Hoffmann, Dushyant V. Sahani
Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts, United States of America
Udo Hoffmann, Christopher J. O'Donnell
Division of Cardiology, Massachusetts General Hospital, Boston, Massachusetts, United States of America
Shih-Jen Hwang, Joseph M. Massaro, Christopher J. O'Donnell, Caroline S. Fox
Framingham Heart Study, National Heart, Lung, and Blood Institute (NHLBI), Framingham, Massachusetts, United States of America
Joseph M. Massaro
Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, United States of America
Christopher J. O'Donnell, Caroline S. Fox
Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland, United States of America
Veikko Salomaa
Chronic Disease Epidemiology Unit, Department of Health Promotion and Chronic Disease Prevention, National Public Health Institute, Helsinki, Finland
Eric E. Schadt
Pacific Biosciences, Menlo Park, California, United States of America
Stephen M. Schwartz, David S. Siscovick
Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology, University of Washington, Seattle, Washington, United States of America
Stephen M. Schwartz
Department of Epidemiology, University of Washington, Seattle, Washington, United States of America
J. Jeffrey Carr
Departments of Radiologic Sciences, Internal Medicine-Cardiology, and Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States of America
Joel N. Hirschhorn
Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America

Corresponding Authors

Competing Interests

Eric E. Schadt is an employee of Pacific Biosciences.

Author Contributions

Conceived and designed the experiments: EKS CJO CSF WHLK JNH IBB. Performed the experiments: EKS LMYA JW RH JLB MFF. Analyzed the data: EKS LMYA JW RH CDP GE MEG LJL MAN SJH JMM BFV AVS. Contributed reagents/materials/analysis tools: EKS VG JMC BDM ARS MT UH JMM CJO DVS VS EES SMS DSS NASH CRN GIANT Consortium MAGIC Investigators JJC TBH CSF WHLK JNH IBB. Wrote the paper: EKS LMYA JW RH LJK CSF WHLK JNH IBB GOLD Consortium.