An Integration of Genome-Wide Association Study and Gene Expression Profiling to Prioritize the Discovery of Novel Susceptibility Loci for Osteoporosis-Related Traits

Yi-Hsiang Hsu; M. Carola Zillikens; Scott G. Wilson; Charles R. Farber; Serkalem Demissie; Nicole Soranzo; Estelle N. Bianchi; Elin Grundberg; Liming Liang; J. Brent Richards; Karol Estrada; Yanhua Zhou; Atila van Nas; Miriam F. Moffatt; Guangju Zhai; Albert Hofman; Joyce B. van Meurs; Huibert A. P. Pols; Roger I. Price; Olle Nilsson; Tomi Pastinen; L. Adrienne Cupples; Aldons J. Lusis; Eric E. Schadt; Serge Ferrari; André G. Uitterlinden; Fernando Rivadeneira; Timothy D. Spector; David Karasik; Douglas P. Kiel

doi:10.1371/journal.pgen.1000977

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Research Article

An Integration of Genome-Wide Association Study and Gene Expression Profiling to Prioritize the Discovery of Novel Susceptibility Loci for Osteoporosis-Related Traits

Yi-Hsiang Hsu ,

Contributed equally to this work with: Yi-Hsiang Hsu, M. Carola Zillikens, Scott G. Wilson, Charles R. Farber, Fernando Rivadeneira, Timothy D. Spector, David Karasik, Douglas P. Kiel

Affiliations Hebrew SeniorLife Institute for Aging Research and Harvard Medical School, Boston, Massachusetts, United States of America, Molecular and Integrative Physiological Sciences Program, Harvard School of Public Health, Boston, Massachusetts, United States of America, Framingham Heart Study, Framingham, Massachusetts, United States of America
⨯
M. Carola Zillikens ,

Contributed equally to this work with: Yi-Hsiang Hsu, M. Carola Zillikens, Scott G. Wilson, Charles R. Farber, Fernando Rivadeneira, Timothy D. Spector, David Karasik, Douglas P. Kiel

Affiliations Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands, Netherlands Genomics Initiative, The Hague, The Netherlands
⨯
Scott G. Wilson ,

Contributed equally to this work with: Yi-Hsiang Hsu, M. Carola Zillikens, Scott G. Wilson, Charles R. Farber, Fernando Rivadeneira, Timothy D. Spector, David Karasik, Douglas P. Kiel

Affiliations Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom, Departments of Endocrinology, Diabetes, and Medical Technology and Physics, Sir Charles Gairdner Hospital, Perth, Australia, School of Medicine and Pharmacology, University of Western Australia, Crawley, Australia
⨯
Charles R. Farber ,

Contributed equally to this work with: Yi-Hsiang Hsu, M. Carola Zillikens, Scott G. Wilson, Charles R. Farber, Fernando Rivadeneira, Timothy D. Spector, David Karasik, Douglas P. Kiel

Affiliation Department of Medicine, Division of Cardiovascular Medicine and Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, United States of America
⨯
Serkalem Demissie,

Affiliations Framingham Heart Study, Framingham, Massachusetts, United States of America, Department of Biostatistics, School of Public Health, Boston University, Boston, Massachusetts, United States of America
⨯
Nicole Soranzo,

Affiliations Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom, Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom
⨯
Estelle N. Bianchi,

Affiliation Service of Bone Diseases, Department of Rehabilitation and Geriatrics, University Geneva Hospital, Geneva, Switzerland
⨯
Elin Grundberg,

Affiliations Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom, Department of Human Genetics, McGill University, Montreal, Canada, McGill University and Genome Quebec Innovation Center, Montreal, Canada
⨯
Liming Liang,

Affiliation Department of Epidemiology, Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, United States of America
⨯
J. Brent Richards,

Affiliations Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom, Department of Human Genetics, McGill University, Montreal, Canada, Departments of Medicine, Human Genetics, and Epidemiology and Biostatistics, Jewish General Hospital, McGill University, Montreal, Canada
⨯
Karol Estrada,

Affiliations Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands, Netherlands Genomics Initiative, The Hague, The Netherlands
⨯
Yanhua Zhou,

Affiliations Framingham Heart Study, Framingham, Massachusetts, United States of America, Department of Biostatistics, School of Public Health, Boston University, Boston, Massachusetts, United States of America
⨯
Atila van Nas,

Affiliation Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America
⨯
Miriam F. Moffatt,

Affiliation National Heart and Lung Institute, Imperial College London, London, United Kingdom
⨯
Guangju Zhai,

Affiliation Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom
⨯
Albert Hofman,

Affiliations Netherlands Genomics Initiative, The Hague, The Netherlands, Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
⨯
Joyce B. van Meurs,

Affiliations Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands, Netherlands Genomics Initiative, The Hague, The Netherlands
⨯
Huibert A. P. Pols,

Affiliations Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands, Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
⨯
Roger I. Price,

Affiliation Departments of Endocrinology, Diabetes, and Medical Technology and Physics, Sir Charles Gairdner Hospital, Perth, Australia
⨯
Olle Nilsson,

Affiliation Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
⨯
Tomi Pastinen,

Affiliations Department of Human Genetics, McGill University, Montreal, Canada, McGill University and Genome Quebec Innovation Center, Montreal, Canada
⨯
L. Adrienne Cupples,

Affiliations Framingham Heart Study, Framingham, Massachusetts, United States of America, Department of Biostatistics, School of Public Health, Boston University, Boston, Massachusetts, United States of America
⨯
Aldons J. Lusis,

Affiliation Departments of Medicine, Human Genetics, Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, Molecular Biology Institute, University of California Los Angeles, Los Angeles, California, United States of America
⨯
Eric E. Schadt,

Affiliation Rosetta Inpharmatics/Merck, Seattle, Washington, United States of America
⨯
Serge Ferrari,

Affiliation Service of Bone Diseases, Department of Rehabilitation and Geriatrics, University Geneva Hospital, Geneva, Switzerland
⨯
André G. Uitterlinden,

Affiliations Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands, Netherlands Genomics Initiative, The Hague, The Netherlands, Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
⨯
Fernando Rivadeneira ,

Contributed equally to this work with: Yi-Hsiang Hsu, M. Carola Zillikens, Scott G. Wilson, Charles R. Farber, Fernando Rivadeneira, Timothy D. Spector, David Karasik, Douglas P. Kiel

Affiliations Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands, Netherlands Genomics Initiative, The Hague, The Netherlands, Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
⨯
Timothy D. Spector ,

Contributed equally to this work with: Yi-Hsiang Hsu, M. Carola Zillikens, Scott G. Wilson, Charles R. Farber, Fernando Rivadeneira, Timothy D. Spector, David Karasik, Douglas P. Kiel

Affiliation Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom
⨯
David Karasik ,

Contributed equally to this work with: Yi-Hsiang Hsu, M. Carola Zillikens, Scott G. Wilson, Charles R. Farber, Fernando Rivadeneira, Timothy D. Spector, David Karasik, Douglas P. Kiel

* E-mail: kiel@hrca.harvard.edu (DPK); karasik@hrca.harvard.edu (DK)

Affiliations Hebrew SeniorLife Institute for Aging Research and Harvard Medical School, Boston, Massachusetts, United States of America, Framingham Heart Study, Framingham, Massachusetts, United States of America
⨯
[ ... ],
Douglas P. Kiel

Contributed equally to this work with: Yi-Hsiang Hsu, M. Carola Zillikens, Scott G. Wilson, Charles R. Farber, Fernando Rivadeneira, Timothy D. Spector, David Karasik, Douglas P. Kiel

* E-mail: kiel@hrca.harvard.edu (DPK); karasik@hrca.harvard.edu (DK)

Affiliations Hebrew SeniorLife Institute for Aging Research and Harvard Medical School, Boston, Massachusetts, United States of America, Framingham Heart Study, Framingham, Massachusetts, United States of America
⨯
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An Integration of Genome-Wide Association Study and Gene Expression Profiling to Prioritize the Discovery of Novel Susceptibility Loci for Osteoporosis-Related Traits

Yi-Hsiang Hsu,
M. Carola Zillikens,
Scott G. Wilson,
Charles R. Farber,
Serkalem Demissie,
Nicole Soranzo,
Estelle N. Bianchi,
Elin Grundberg,
Liming Liang,
J. Brent Richards

Published: June 10, 2010
https://doi.org/10.1371/journal.pgen.1000977

About the Authors

Yi-Hsiang Hsu

Contributed equally to this work with: Yi-Hsiang Hsu, M. Carola Zillikens, Scott G. Wilson, Charles R. Farber, Fernando Rivadeneira, Timothy D. Spector, David Karasik, Douglas P. Kiel

Affiliations Hebrew SeniorLife Institute for Aging Research and Harvard Medical School, Boston, Massachusetts, United States of America, Molecular and Integrative Physiological Sciences Program, Harvard School of Public Health, Boston, Massachusetts, United States of America, Framingham Heart Study, Framingham, Massachusetts, United States of America

M. Carola Zillikens

Contributed equally to this work with: Yi-Hsiang Hsu, M. Carola Zillikens, Scott G. Wilson, Charles R. Farber, Fernando Rivadeneira, Timothy D. Spector, David Karasik, Douglas P. Kiel

Affiliations Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands, Netherlands Genomics Initiative, The Hague, The Netherlands

Scott G. Wilson

Contributed equally to this work with: Yi-Hsiang Hsu, M. Carola Zillikens, Scott G. Wilson, Charles R. Farber, Fernando Rivadeneira, Timothy D. Spector, David Karasik, Douglas P. Kiel

Affiliations Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom, Departments of Endocrinology, Diabetes, and Medical Technology and Physics, Sir Charles Gairdner Hospital, Perth, Australia, School of Medicine and Pharmacology, University of Western Australia, Crawley, Australia

Charles R. Farber

Contributed equally to this work with: Yi-Hsiang Hsu, M. Carola Zillikens, Scott G. Wilson, Charles R. Farber, Fernando Rivadeneira, Timothy D. Spector, David Karasik, Douglas P. Kiel

Affiliation Department of Medicine, Division of Cardiovascular Medicine and Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, United States of America

Serkalem Demissie

Affiliations Framingham Heart Study, Framingham, Massachusetts, United States of America, Department of Biostatistics, School of Public Health, Boston University, Boston, Massachusetts, United States of America

Nicole Soranzo

Affiliations Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom, Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom

Estelle N. Bianchi

Affiliation Service of Bone Diseases, Department of Rehabilitation and Geriatrics, University Geneva Hospital, Geneva, Switzerland

Elin Grundberg

Affiliations Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom, Department of Human Genetics, McGill University, Montreal, Canada, McGill University and Genome Quebec Innovation Center, Montreal, Canada

Liming Liang

Affiliation Department of Epidemiology, Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, United States of America

J. Brent Richards

Affiliations Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom, Department of Human Genetics, McGill University, Montreal, Canada, Departments of Medicine, Human Genetics, and Epidemiology and Biostatistics, Jewish General Hospital, McGill University, Montreal, Canada

Karol Estrada

Affiliations Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands, Netherlands Genomics Initiative, The Hague, The Netherlands

Yanhua Zhou

Atila van Nas

Affiliation Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America

Miriam F. Moffatt

Affiliation National Heart and Lung Institute, Imperial College London, London, United Kingdom

Guangju Zhai

Affiliation Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom

Albert Hofman

Affiliations Netherlands Genomics Initiative, The Hague, The Netherlands, Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands

Joyce B. van Meurs

Affiliations Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands, Netherlands Genomics Initiative, The Hague, The Netherlands

Huibert A. P. Pols

Affiliations Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands, Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands

Roger I. Price

Affiliation Departments of Endocrinology, Diabetes, and Medical Technology and Physics, Sir Charles Gairdner Hospital, Perth, Australia

Olle Nilsson

Affiliation Department of Surgical Sciences, Uppsala University, Uppsala, Sweden

Tomi Pastinen

Affiliations Department of Human Genetics, McGill University, Montreal, Canada, McGill University and Genome Quebec Innovation Center, Montreal, Canada

L. Adrienne Cupples

Aldons J. Lusis

Affiliation Departments of Medicine, Human Genetics, Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, Molecular Biology Institute, University of California Los Angeles, Los Angeles, California, United States of America

Eric E. Schadt

Affiliation Rosetta Inpharmatics/Merck, Seattle, Washington, United States of America

Serge Ferrari

Affiliation Service of Bone Diseases, Department of Rehabilitation and Geriatrics, University Geneva Hospital, Geneva, Switzerland

André G. Uitterlinden

Affiliations Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands, Netherlands Genomics Initiative, The Hague, The Netherlands, Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands

Fernando Rivadeneira

Contributed equally to this work with: Yi-Hsiang Hsu, M. Carola Zillikens, Scott G. Wilson, Charles R. Farber, Fernando Rivadeneira, Timothy D. Spector, David Karasik, Douglas P. Kiel

Timothy D. Spector

Contributed equally to this work with: Yi-Hsiang Hsu, M. Carola Zillikens, Scott G. Wilson, Charles R. Farber, Fernando Rivadeneira, Timothy D. Spector, David Karasik, Douglas P. Kiel

Affiliation Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom

David Karasik

Contributed equally to this work with: Yi-Hsiang Hsu, M. Carola Zillikens, Scott G. Wilson, Charles R. Farber, Fernando Rivadeneira, Timothy D. Spector, David Karasik, Douglas P. Kiel

* E-mail: kiel@hrca.harvard.edu (DPK); karasik@hrca.harvard.edu (DK)

Affiliations Hebrew SeniorLife Institute for Aging Research and Harvard Medical School, Boston, Massachusetts, United States of America, Framingham Heart Study, Framingham, Massachusetts, United States of America

Douglas P. Kiel

Contributed equally to this work with: Yi-Hsiang Hsu, M. Carola Zillikens, Scott G. Wilson, Charles R. Farber, Fernando Rivadeneira, Timothy D. Spector, David Karasik, Douglas P. Kiel

* E-mail: kiel@hrca.harvard.edu (DPK); karasik@hrca.harvard.edu (DK)

Competing Interests

The authors have declared that no competing interests exist.

Author Contributions

Conceived and designed the experiments: YHH SGW CRF AvN MFM AH JBvM HAPP RIP ON TP LAC AJL SF AGU TDS DK DPK. Performed the experiments: YHH CRF ENB LL AvN RIP ON TP EES SF. Analyzed the data: YHH MCZ SGW CRF SD NS ENB EG LL JBR KE YZ GZ EES SF FR. Contributed reagents/materials/analysis tools: EES. Wrote the paper: YHH MCZ SGW CRF DK DPK. Provided comments and suggestions for the manuscript: CRF SD ENB LL JBR KE LAC SF AGU FR TDS DK DPK. Interpreted results: FR TDS DK DPK. Edited manuscript: DK DPK.

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