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Whole‐genome sequencing identifies EN1 as a determinant of bone density and fracture

Author

Listed:
  • Hou‐Feng Zheng

    (Human Genetics, Epidemiology and Biostatistics, McGill University
    Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University)

  • Vincenzo Forgetta

    (Human Genetics, Epidemiology and Biostatistics, McGill University
    Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University)

  • Yi‐Hsiang Hsu

    (Institute for Aging Research, Hebrew SeniorLife
    Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Karol Estrada

    (Harvard Medical School
    Broad Institute of MIT and Harvard
    Erasmus Medical Center
    Analytic and Translational Genetics Unit, Massachusetts General Hospital)

  • Alberto Rosello‐Diez

    (Developmental Biology Program, Sloan Kettering Institute)

  • Paul J. Leo

    (The University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital)

  • Chitra L. Dahia

    (Weill Cornell Medical College
    Tissue Engineering, Regeneration and Repair Program, Hospital for Special Surgery)

  • Kyung Hyun Park‐Min

    (Rheumatology Divison, Hospital for Special Surgery New York)

  • Jonathan H. Tobias

    (School of Clinical Science, University of Bristol
    MRC Integrative Epidemiology Unit, University of Bristol)

  • Charles Kooperberg

    (Fred Hutchinson Cancer Research Center)

  • Aaron Kleinman

    (23andMe)

  • Unnur Styrkarsdottir

    (deCODE Genetics)

  • Ching‐Ti Liu

    (Boston University School of Public Health)

  • Charlotta Uggla

    (Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg)

  • Daniel S. Evans

    (California Pacific Medical Center Research Institute)

  • Carrie M. Nielson

    (Oregon Health & Science University
    Bone & Mineral Unit, Oregon Health & Science University)

  • Klaudia Walter

    (Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus)

  • Ulrika Pettersson‐Kymmer

    (Umeå University
    Umeå University)

  • Shane McCarthy

    (Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus)

  • Joel Eriksson

    (Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg
    Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg)

  • Tony Kwan

    (McGill University and Genome Quebec Innovation Centre)

  • Mila Jhamai

    (Erasmus Medical Center)

  • Katerina Trajanoska

    (Erasmus Medical Center
    Erasmus Medical Center)

  • Yasin Memari

    (Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus)

  • Josine Min

    (MRC Integrative Epidemiology Unit, University of Bristol)

  • Jie Huang

    (Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus)

  • Petr Danecek

    (Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus)

  • Beth Wilmot

    (Oregon Clinical and Translational Research Institute, Oregon Health & Science University
    Oregon Health & Science University)

  • Rui Li

    (Human Genetics, Epidemiology and Biostatistics, McGill University
    Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University)

  • Wen‐Chi Chou

    (Institute for Aging Research, Hebrew SeniorLife
    Harvard Medical School)

  • Lauren E. Mokry

    (Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University)

  • Alireza Moayyeri

    (Farr Institute of Health Informatics Research, University College London
    King’s College London)

  • Melina Claussnitzer

    (Institute for Aging Research, Hebrew SeniorLife
    Harvard Medical School
    Broad Institute of MIT and Harvard
    Beth Israel Deaconess Medical Center)

  • Chia‐Ho Cheng

    (Institute for Aging Research, Hebrew SeniorLife)

  • Warren Cheung

    (McGill University and Genome Quebec Innovation Centre
    McGill University)

  • Carolina Medina‐Gómez

    (Erasmus Medical Center
    Erasmus Medical Center
    Netherlands Genomics Initiative (NGI)‐sponsored Netherlands Consortium for Healthy Aging (NCHA))

  • Bing Ge

    (McGill University and Genome Quebec Innovation Centre)

  • Shu‐Huang Chen

    (McGill University and Genome Quebec Innovation Centre)

  • Kwangbom Choi

    (Center for Musculoskeletal Research, University of Rochester)

  • Ling Oei

    (Erasmus Medical Center
    Erasmus Medical Center
    Netherlands Genomics Initiative (NGI)‐sponsored Netherlands Consortium for Healthy Aging (NCHA))

  • James Fraser

    (McGill University)

  • Robert Kraaij

    (Erasmus Medical Center
    Erasmus Medical Center
    Netherlands Genomics Initiative (NGI)‐sponsored Netherlands Consortium for Healthy Aging (NCHA))

  • Matthew A. Hibbs

    (Center for Musculoskeletal Research, University of Rochester
    Trinity University)

  • Celia L. Gregson

    (Musculoskeletal Research Unit, University of Bristol)

  • Denis Paquette

    (McGill University)

  • Albert Hofman

    (Erasmus Medical Center
    Netherlands Genomics Initiative (NGI)‐sponsored Netherlands Consortium for Healthy Aging (NCHA))

  • Carl Wibom

    (Umeå University)

  • Gregory J. Tranah

    (Oregon Health & Science University
    Bone & Mineral Unit, Oregon Health & Science University)

  • Mhairi Marshall

    (The University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital)

  • Brooke B. Gardiner

    (The University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital)

  • Katie Cremin

    (The University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital)

  • Paul Auer

    (School of Public Health, University of Wisconsin)

  • Li Hsu

    (Fred Hutchinson Cancer Research Center)

  • Sue Ring

    (School of Social and Community Medicine, University of Bristol)

  • Joyce Y. Tung

    (23andMe)

  • Gudmar Thorleifsson

    (deCODE Genetics)

  • Anke W. Enneman

    (Erasmus Medical Center)

  • Natasja M. van Schoor

    (VU University Medical Center)

  • Lisette C. P. G. M. de Groot

    (Wageningen University)

  • Nathalie van der Velde

    (Erasmus Medical Center
    Section Geriatrics, Academic Medical Center)

  • Beatrice Melin

    (Umeå University)

  • John P. Kemp

    (The University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital
    MRC Integrative Epidemiology Unit, University of Bristol)

  • Claus Christiansen

    (Nordic Bioscience)

  • Adrian Sayers

    (Musculoskeletal Research Unit, University of Bristol)

  • Yanhua Zhou

    (Boston University School of Public Health)

  • Sophie Calderari

    (Cordeliers Research Centre
    Institute of Cardiometabolism and Nutrition, University Pierre & Marie Curie)

  • Jeroen van Rooij

    (Erasmus Medical Center
    Netherlands Genomics Initiative (NGI)‐sponsored Netherlands Consortium for Healthy Aging (NCHA))

  • Chris Carlson

    (Fred Hutchinson Cancer Research Center)

  • Ulrike Peters

    (Fred Hutchinson Cancer Research Center)

  • Soizik Berlivet

    (McGill University)

  • Josée Dostie

    (McGill University)

  • Andre G. Uitterlinden

    (Erasmus Medical Center
    Erasmus Medical Center
    Netherlands Genomics Initiative (NGI)‐sponsored Netherlands Consortium for Healthy Aging (NCHA))

  • Stephen R. Williams

    (Centre for Public Health Genomics, University of Virginia)

  • Charles Farber

    (Centre for Public Health Genomics, University of Virginia)

  • Daniel Grinberg

    (University of Barcelona
    U‐720, Centre for Biomedical Network Research on Rare Diseases (CIBERER)
    The Institute of Biomedicine of the University of Barcelona (IBUB))

  • Andrea Z. LaCroix

    (Women’s Health Center of Excellence Family Medicine and Public Health, University of California – San Diego, San Diego
    92093)

  • Jeff Haessler

    (Fred Hutchinson Cancer Research Center)

  • Daniel I. Chasman

    (Harvard Medical School
    Brigham and Women’s Hospital)

  • Franco Giulianini

    (Brigham and Women’s Hospital)

  • Lynda M. Rose

    (Brigham and Women’s Hospital)

  • Paul M. Ridker

    (Harvard Medical School
    Brigham and Women’s Hospital)

  • John A. Eisman

    (Osteoporosis & Bone Biology Program, Garvan Institute of Medical Research
    School of Medicine Sydney, University of Notre Dame Australia
    St. Vincent’s Hospital & Clinical School, NSW University)

  • Tuan V. Nguyen

    (Osteoporosis & Bone Biology Program, Garvan Institute of Medical Research
    St. Vincent’s Hospital & Clinical School, NSW University)

  • Jacqueline R. Center

    (Osteoporosis & Bone Biology Program, Garvan Institute of Medical Research
    St. Vincent’s Hospital & Clinical School, NSW University)

  • Xavier Nogues

    (Musculoskeletal Research Group, Institut Hospital del Mar d’Investigacions Mèdiques
    Cooperative Research Network on Aging and Fragility (RETICEF), Institute of Health Carlos III
    Hospital del Mar, Universitat Autònoma de Barcelona)

  • Natalia Garcia‐Giralt

    (Musculoskeletal Research Group, Institut Hospital del Mar d’Investigacions Mèdiques
    Cooperative Research Network on Aging and Fragility (RETICEF), Institute of Health Carlos III)

  • Lenore L. Launer

    (Neuroepidemiology Section, National Institute on Aging, National Institutes of Health)

  • Vilmunder Gudnason

    (Icelandic Heart Association
    Faculty of Medicine, University of Iceland)

  • Dan Mellström

    (Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg)

  • Liesbeth Vandenput

    (Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg)

  • Najaf Amin

    (Genetic epidemiology unit, Erasmus MC)

  • Cornelia M. van Duijn

    (Genetic epidemiology unit, Erasmus MC)

  • Magnus K. Karlsson

    (Skåne University Hospital Malmö)

  • Östen Ljunggren

    (University of Uppsala)

  • Olle Svensson

    (Umeå Unviersity)

  • Göran Hallmans

    (Umeå University)

  • François Rousseau

    (Medical Biochemistry and Pathology, Université Laval
    Axe Santé des Populations et Pratiques Optimales en Santé, Centre de recherche du CHU de Québec)

  • Sylvie Giroux

    (Axe Santé des Populations et Pratiques Optimales en Santé, Centre de recherche du CHU de Québec)

  • Johanne Bussière

    (Axe Santé des Populations et Pratiques Optimales en Santé, Centre de recherche du CHU de Québec)

  • Pascal P. Arp

    (Erasmus Medical Center)

  • Fjorda Koromani

    (Erasmus Medical Center
    Erasmus Medical Center)

  • Richard L. Prince

    (Sir Charles Gairdner Hospital
    University of Western Australia)

  • Joshua R. Lewis

    (Sir Charles Gairdner Hospital
    University of Western Australia)

  • Bente L. Langdahl

    (Aarhus University Hospital)

  • A. Pernille Hermann

    (Odense University Hospital)

  • Jens‐Erik B. Jensen

    (Hvidovre University Hospital)

  • Stephen Kaptoge

    (Farr Institute of Health Informatics Research, University College London)

  • Kay‐Tee Khaw

    (Clinical Gerontology Unit, University of Cambridge)

  • Jonathan Reeve

    (Medicine and Public Health and Primary Care, University of Cambridge
    Institute of Musculoskeletal Sciences, The Botnar Research Centre, University of Oxford)

  • Melissa M. Formosa

    (Faculty of Health Sciences, University of Malta)

  • Angela Xuereb‐Anastasi

    (Faculty of Health Sciences, University of Malta)

  • Kristina Åkesson

    (Skåne University Hospital Malmö
    Clinical and Molecular Osteoporosis Research Unit, Lund University)

  • Fiona E. McGuigan

    (Clinical and Molecular Osteoporosis Research Unit, Lund University)

  • Gaurav Garg

    (Clinical and Molecular Osteoporosis Research Unit, Lund University)

  • Jose M. Olmos

    (University of Cantabria
    Hospital U.M. Valdecilla‐ IDIVAL)

  • Maria T. Zarrabeitia

    (University of Cantabria)

  • Jose A. Riancho

    (University of Cantabria
    Hospital U.M. Valdecilla‐ IDIVAL)

  • Stuart H. Ralston

    (Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh)

  • Nerea Alonso

    (Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh)

  • Xi Jiang

    (College of Dental Medicine, University of Connecticut Health Center)

  • David Goltzman

    (McGill University)

  • Tomi Pastinen

    (McGill University and Genome Quebec Innovation Centre
    McGill University)

  • Elin Grundberg

    (McGill University and Genome Quebec Innovation Centre
    McGill University)

  • Dominique Gauguier

    (Cordeliers Research Centre
    Institute of Cardiometabolism and Nutrition, University Pierre & Marie Curie)

  • Eric S. Orwoll

    (Bone & Mineral Unit, Oregon Health & Science University
    Oregon Health & Science University)

  • David Karasik

    (Institute for Aging Research, Hebrew SeniorLife
    Faculty of Medicine in the Galilee, Bar-Ilan University)

  • George Davey‐Smith

    (MRC Integrative Epidemiology Unit, University of Bristol)

  • Albert V. Smith

    (Icelandic Heart Association
    Faculty of Medicine, University of Iceland)

  • Kristin Siggeirsdottir

    (Icelandic Heart Association)

  • Tamara B. Harris

    (Laboratory of Epidemiology, National Institute on Aging, National Institutes of Health)

  • M. Carola Zillikens

    (Erasmus Medical Center)

  • Joyce B. J. van Meurs

    (Erasmus Medical Center
    Erasmus Medical Center)

  • Unnur Thorsteinsdottir

    (deCODE Genetics
    Faculty of Medicine, University of Iceland)

  • Matthew T. Maurano

    (University of Washington)

  • Nicholas J. Timpson

    (MRC Integrative Epidemiology Unit, University of Bristol)

  • Nicole Soranzo

    (Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus)

  • Richard Durbin

    (Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus)

  • Scott G. Wilson

    (King’s College London
    Sir Charles Gairdner Hospital
    School of Medicine and Pharmacology, University of Western Australia)

  • Evangelia E. Ntzani

    (University of Ioannina School of Medicine
    Policy and Practice, Brown University School of Public Health, Providence)

  • Matthew A. Brown

    (The University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital)

  • Kari Stefansson

    (Faculty of Medicine, University of Iceland
    deCODE Genetics)

  • David A. Hinds

    (23andMe)

  • Tim Spector

    (King’s College London)

  • L. Adrienne Cupples

    (Boston University School of Public Health
    Framingham Heart Study)

  • Claes Ohlsson

    (Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg)

  • Celia M. T. Greenwood

    (Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University
    McGill University
    Biostatistics and Occupational Health, McGill University
    Gerald Bronfman Centre, McGill University)

  • Rebecca D. Jackson

    (Diabetes and Metabolism, The Ohio State University)

  • David W. Rowe

    (College of Dental Medicine, University of Connecticut Health Center)

  • Cynthia A. Loomis

    (New York University School of Medicine)

  • David M. Evans

    (The University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital
    MRC Integrative Epidemiology Unit, University of Bristol)

  • Cheryl L. Ackert‐Bicknell

    (Center for Musculoskeletal Research, University of Rochester)

  • Alexandra L. Joyner

    (Developmental Biology Program, Sloan Kettering Institute)

  • Emma L. Duncan

    (The University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital
    Royal Brisbane and Women’s Hospital)

  • Douglas P. Kiel

    (Institute for Aging Research, Hebrew SeniorLife
    Harvard Medical School
    Broad Institute of MIT and Harvard
    Beth Israel Deaconess Medical Center)

  • Fernando Rivadeneira

    (Erasmus Medical Center
    Erasmus Medical Center
    Netherlands Genomics Initiative (NGI)‐sponsored Netherlands Consortium for Healthy Aging (NCHA))

  • J. Brent Richards

    (Human Genetics, Epidemiology and Biostatistics, McGill University
    Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University
    King’s College London)

Abstract

Human population genomic studies, including whole‐genome sequencing, were undertaken to identify determinants of bone mineral density (BMD), a major predictor of osteoporotic fractures. Non‐coding variants with large effects on BMD and fractures were identified near the EN1 locus and mouse studies confirmed this gene has an important role in skeletal biology.

Suggested Citation

  • Hou‐Feng Zheng & Vincenzo Forgetta & Yi‐Hsiang Hsu & Karol Estrada & Alberto Rosello‐Diez & Paul J. Leo & Chitra L. Dahia & Kyung Hyun Park‐Min & Jonathan H. Tobias & Charles Kooperberg & Aaron Kleinm, 2015. "Whole‐genome sequencing identifies EN1 as a determinant of bone density and fracture," Nature, Nature, vol. 526(7571), pages 112-117, October.
    • Handle: RePEc:nat:nature:v:526:y:2015:i:7571:d:10.1038_nature14878
    DOI: 10.1038/nature14878
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    Cited by:

    1. Hong Zhang & Zheyang Wu, 2023. "The generalized Fisher's combination and accurate p‐value calculation under dependence," Biometrics, The International Biometric Society, vol. 79(2), pages 1159-1172, June.

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