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

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 Kleinman, Unnur Styrkarsdottir, Ching‐Ti Liu, Charlotta Uggla, Daniel S. Evans, Carrie M. Nielson, Klaudia Walter, Ulrika Pettersson‐Kymmer, Shane McCarthy, Joel Eriksson, Tony Kwan, Mila Jhamai, Katerina Trajanoska, Yasin Memari, Josine Min, Jie Huang, Petr Danecek, Beth Wilmot, Rui Li, Wen‐Chi Chou, Lauren E. Mokry, Alireza Moayyeri, Melina Claussnitzer, Chia‐Ho Cheng, Warren Cheung, Carolina Medina‐Gómez, Bing Ge, Shu‐Huang Chen, Kwangbom Choi, Ling Oei, James Fraser, Robert Kraaij, Matthew A. Hibbs, Celia L. Gregson, Denis Paquette, Albert Hofman, Carl Wibom, Gregory J. Tranah, Mhairi Marshall, Brooke B. Gardiner, Katie Cremin, Paul Auer, Li Hsu, Sue Ring, Joyce Y. Tung, Gudmar Thorleifsson, Anke W. Enneman, Natasja M. van Schoor, Lisette C. P. G. M. de Groot, Nathalie van der Velde, Beatrice Melin, John P. Kemp, Claus Christiansen, Adrian Sayers, Yanhua Zhou, Sophie Calderari, Jeroen van Rooij, Chris Carlson, Ulrike Peters, Soizik Berlivet, Josée Dostie, Andre G. Uitterlinden, Stephen R. Williams, Charles Farber, Daniel Grinberg, Andrea Z. LaCroix, Jeff Haessler, Daniel I. Chasman, Franco Giulianini, Lynda M. Rose, Paul M. Ridker, John A. Eisman, Tuan V. Nguyen, Jacqueline R. Center, Xavier Nogues, Natalia Garcia‐Giralt, Lenore L. Launer, Vilmunder Gudnason, Dan Mellström, Liesbeth Vandenput, Najaf Amin, Cornelia M. van Duijn, Magnus K. Karlsson, Östen Ljunggren, Olle Svensson, Göran Hallmans, François Rousseau, Sylvie Giroux, Johanne Bussière, Pascal P. Arp, Fjorda Koromani, Richard L. Prince, Joshua R. Lewis, Bente L. Langdahl, A. Pernille Hermann, Jens‐Erik B. Jensen, Stephen Kaptoge, Kay‐Tee Khaw, Jonathan Reeve, Melissa M. Formosa, Angela Xuereb‐Anastasi, Kristina Åkesson, Fiona E. McGuigan, Gaurav Garg, Jose M. Olmos, Maria T. Zarrabeitia, Jose A. Riancho, Stuart H. Ralston, Nerea Alonso, Xi Jiang, David Goltzman, Tomi Pastinen, Elin Grundberg, Dominique Gauguier, Eric S. Orwoll, David Karasik, George Davey‐Smith, Albert V. Smith, Kristin Siggeirsdottir, Tamara B. Harris, M. Carola Zillikens, Joyce B. J. van Meurs, Unnur Thorsteinsdottir, Matthew T. Maurano, Nicholas J. Timpson, Nicole Soranzo, Richard Durbin, Scott G. Wilson, Evangelia E. Ntzani, Matthew A. Brown, Kari Stefansson, David A. Hinds, Tim Spector, L. Adrienne Cupples, Claes Ohlsson, Celia M. T. Greenwood, Rebecca D. Jackson, David W. Rowe, Cynthia A. Loomis, David M. Evans, Cheryl L. Ackert‐Bicknell, Alexandra L. Joyner, Emma L. Duncan, Douglas P. Kiel, Fernando Rivadeneira and J. Brent Richards ()
Additional contact information
Hou‐Feng Zheng: Human Genetics, Epidemiology and Biostatistics, McGill University
Vincenzo Forgetta: Human Genetics, Epidemiology and Biostatistics, McGill University
Yi‐Hsiang Hsu: Institute for Aging Research, Hebrew SeniorLife
Karol Estrada: Harvard Medical School
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
Kyung Hyun Park‐Min: Rheumatology Divison, Hospital for Special Surgery New York
Jonathan H. Tobias: School of Clinical Science, 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
Klaudia Walter: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus
Ulrika Pettersson‐Kymmer: 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
Tony Kwan: McGill University and Genome Quebec Innovation Centre
Mila Jhamai: Erasmus Medical Center
Katerina Trajanoska: 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
Rui Li: Human Genetics, Epidemiology and Biostatistics, McGill University
Wen‐Chi Chou: Institute for Aging Research, Hebrew SeniorLife
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
Melina Claussnitzer: Institute for Aging Research, Hebrew SeniorLife
Chia‐Ho Cheng: Institute for Aging Research, Hebrew SeniorLife
Warren Cheung: McGill University and Genome Quebec Innovation Centre
Carolina Medina‐Gómez: Erasmus Medical Center
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
James Fraser: McGill University
Robert Kraaij: Erasmus Medical Center
Matthew A. Hibbs: Center for Musculoskeletal Research, University of Rochester
Celia L. Gregson: Musculoskeletal Research Unit, University of Bristol
Denis Paquette: McGill University
Albert Hofman: Erasmus Medical Center
Carl Wibom: Umeå University
Gregory J. Tranah: 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
Beatrice Melin: Umeå University
John P. Kemp: The University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital
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
Jeroen van Rooij: Erasmus Medical Center
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
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
Andrea Z. LaCroix: Women’s Health Center of Excellence Family Medicine and Public Health, University of California – San Diego, San Diego
Jeff Haessler: Fred Hutchinson Cancer Research Center
Daniel I. Chasman: Harvard Medical School
Franco Giulianini: Brigham and Women’s Hospital
Lynda M. Rose: Brigham and Women’s Hospital
Paul M. Ridker: Harvard Medical School
John A. Eisman: Osteoporosis & Bone Biology Program, Garvan Institute of Medical Research
Tuan V. Nguyen: Osteoporosis & Bone Biology Program, Garvan Institute of Medical Research
Jacqueline R. Center: Osteoporosis & Bone Biology Program, Garvan Institute of Medical Research
Xavier Nogues: Musculoskeletal Research Group, Institut Hospital del Mar d’Investigacions Mèdiques
Natalia Garcia‐Giralt: Musculoskeletal Research Group, Institut Hospital del Mar d’Investigacions Mèdiques
Lenore L. Launer: Neuroepidemiology Section, National Institute on Aging, National Institutes of Health
Vilmunder Gudnason: Icelandic Heart Association
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
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
Richard L. Prince: Sir Charles Gairdner Hospital
Joshua R. Lewis: Sir Charles Gairdner Hospital
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
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
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
Maria T. Zarrabeitia: University of Cantabria
Jose A. Riancho: University of Cantabria
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
Elin Grundberg: McGill University and Genome Quebec Innovation Centre
Dominique Gauguier: Cordeliers Research Centre
Eric S. Orwoll: Bone & Mineral Unit, Oregon Health & Science University
David Karasik: Institute for Aging Research, Hebrew SeniorLife
George Davey‐Smith: MRC Integrative Epidemiology Unit, University of Bristol
Albert V. Smith: Icelandic Heart Association
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
Unnur Thorsteinsdottir: deCODE Genetics
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
Evangelia E. Ntzani: University of Ioannina School of Medicine
Matthew A. Brown: The University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital
Kari Stefansson: Faculty of Medicine, University of Iceland
David A. Hinds: 23andMe
Tim Spector: King’s College London
L. Adrienne Cupples: Boston University School of Public Health
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
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
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
Douglas P. Kiel: Institute for Aging Research, Hebrew SeniorLife
Fernando Rivadeneira: Erasmus Medical Center
J. Brent Richards: Human Genetics, Epidemiology and Biostatistics, McGill University

Nature, 2015, vol. 526, issue 7571, 112-117

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.

Date: 2015
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/nature14878 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:526:y:2015:i:7571:d:10.1038_nature14878

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature14878

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().