Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Genome-wide Meta-analysis of 158,000 Individuals of European Ancestry Identifies Three Loci Associated with Chronic Back Pain

Pradeep Suri, Melody R. Palmer, Yakov A. Tsepilov, Maxim B. Freidin, Cindy G. Boer, Michelle S. Yau, Daniel S. Evans, Andrea Gelemanovic, Traci M. Bartz, Maria Nethander, Liubov Arbeeva, Lennart Karssen, Tuhina Neogi, Archie Campbell, Dan Mellstrom, Claes Ohlsson, Lynn M. Marshall, Eric Orwoll, Andre Uitterlinden, Jerome I. Rotter, Gordan Lauc, Bruce M. Psaty, Magnus K Karlsson, Nancy E. Lane, Gail Jarvik, Ozren Polasek, Marc Hochberg, Joanne M. Jordan, Joyce B. J. Van Meurs, Rebecca Jackson, Carrie M. Nielson, Braxton D. Mitchell, Blair H. Smith, Caroline Hayward, Nicholas L. Smith, Yurii S. Aulchenko, Frances M.K. Williams
doi: https://doi.org/10.1101/244483
Pradeep Suri
1Seattle Epidemiologic Research and Information Center (ERIC), Department of Veterans Affairs Office of Research and Development, Seattle, USA
2Division of Rehabilitation Care Services, VA Puget Sound Health Care System, Seattle, USA
3Department of Rehabilitation Medicine, University of Washington, Seattle, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Melody R. Palmer
4Department of Medicine (Medical Genetics), University of Washington, Seattle, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yakov A. Tsepilov
5Polyomica, ‘s-Hertogenbosch, the Netherlands
6Novosibirsk State University, Novosibirsk, Russia
7Institute of Cytology and Genetics SD RAS, Novosibirsk, Russia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Maxim B. Freidin
8Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Cindy G. Boer
9Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michelle S. Yau
10Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA
11Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Daniel S. Evans
12California Pacific Medical Center Research Institute, San Francisco, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andrea Gelemanovic
13Department of Public Health, University of Split Medical School, Split, Croatia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Traci M. Bartz
14Cardiovascular Health Research Unit and Department of Medicine, University of Washington, Seattle, USA
15Department of Biostatistics, University of Washington, Seattle, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Maria Nethander
16Department of Medicine, University of Göteborg, Göteborg, Sweden
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Liubov Arbeeva
17Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lennart Karssen
5Polyomica, ‘s-Hertogenbosch, the Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tuhina Neogi
18Department of Medicine, Clinical Epidemiology Unit, Boston University School of Medicine, Boston, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Archie Campbell
19Centre for Genomic and Experimental Medicine, MRC Institute of Genetics & Molecular Medicine, University of Edinburgh, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dan Mellstrom
20Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Sweden
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Claes Ohlsson
21Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Göteborg, Sweden
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lynn M. Marshall
22Department of Orthopedics and Rehabilitation, Oregon Health and Science University, Portland, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Eric Orwoll
23Department of Medicine, Oregon Health and Science University, Portland, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andre Uitterlinden
9Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jerome I. Rotter
24Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, USA
25Division of Genomic Outcomes, Departments of Pediatrics and Medicine, Harbor-UCLA Medical Center, Torrance, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gordan Lauc
26Genos Ltd, Osijek, Croatia
27Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bruce M. Psaty
14Cardiovascular Health Research Unit and Department of Medicine, University of Washington, Seattle, USA
28Department of Health Services, University of Washington, Seattle, USA
29Department of Epidemiology, University of Washington, Seattle, USA
30Kaiser Permanente Washington Health Research Institute, Kaiser Permanente Washington, Seattle, WA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Magnus K Karlsson
31Department of Orthopedics, Skane University Hospital, Lund University, Malmö, Sweden
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nancy E. Lane
32Departments of Medicine and Rheumatology, University of California Davis, Sacramento, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gail Jarvik
4Department of Medicine (Medical Genetics), University of Washington, Seattle, USA
33Department of Genome Sciences, University of Washington, Seattle, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ozren Polasek
13Department of Public Health, University of Split Medical School, Split, Croatia
34Hospital “Sveti Ivan”, Zagreb, Croatia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Marc Hochberg
35Departments of Medicine and Epidemiology, University of Maryland, Baltimore, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joanne M. Jordan
17Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joyce B. J. Van Meurs
9Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rebecca Jackson
36Department of Medicine, The Ohio State University, Columbus, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Carrie M. Nielson
37School of Public Health, Oregon Health and Science University, Portland, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Braxton D. Mitchell
35Departments of Medicine and Epidemiology, University of Maryland, Baltimore, USA
38Geriatric Research, Education and Clinical Center, Veterans Affairs Medical Center, Baltimore, MD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Blair H. Smith
39Division of Population Health Sciences, School of Medicine, University of Dundee, Dundee, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Caroline Hayward
40MRC Human Genetics Unit, MRC Institute of Genetics & Molecular Medicine, University of Edinburgh, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nicholas L. Smith
1Seattle Epidemiologic Research and Information Center (ERIC), Department of Veterans Affairs Office of Research and Development, Seattle, USA
29Department of Epidemiology, University of Washington, Seattle, USA
30Kaiser Permanente Washington Health Research Institute, Kaiser Permanente Washington, Seattle, WA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yurii S. Aulchenko
5Polyomica, ‘s-Hertogenbosch, the Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Frances M.K. Williams
8Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

ABSTRACT

OBJECTIVES To conduct a genome-wide association study (GWAS) meta-analysis of chronic back pain (CBP).

METHODS Adults of European ancestry were included from 16 cohorts in Europe and North America. CBP cases were defined as those reporting back pain present for >3-6 months; non-cases were included as comparisons (“controls”). Each cohort conducted genotyping using commercially available arrays followed by imputation. GWAS used logistic regression models with additive genetic effects, adjusting for age, sex, study-specific covariates, and population substructure. The threshold for genome-wide significance in the fixed-effect inverse-variance weighted meta-analysis was p<5×10−8. Suggestive (p<5×10−7) and genome-wide significant (p<5×10−8) variants were carried forward for replication or further investigation in an independent sample.

RESULTS The discovery sample was comprised of 158,025 individuals, including 29,531 CBP cases. A genome-wide significant association was found for the intronic variant rs12310519 in SOX5 (OR 1.08, p=7.2×10−10). This was subsequently replicated in an independent sample of 283,752 subjects, including 50,915 cases (OR 1.06, p=5.3×10−11), and exceeded genome-wide significance in joint meta-analysis (OR=1.07, p=4.5×10−19). We found suggestive associations at three other loci in the discovery sample, two of which exceeded genome-wide significance in joint meta-analysis: an intergenic variant, rs7833174, located between CCDC26 and GSDMC (OR 1.05, p=4.4×10−13), and an intronic variant, rs4384683, in DCC (OR 0.97, p=2.4×10−10).

DISCUSSION In this first reported meta-analysis of GWAS for CBP, we identified and replicated a genetic locus associated with CBP (SOX5). We also identified 2 other loci that reached genome-wide significance in a 2-stage joint meta-analysis (CCDC26/GSDMC and DCC).

Footnotes

  • B.M.P. serves on the DSMB of a clinical trial funded by Zoll LifeCor and on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson; Y.S.A. and L.K. are founders and co-owners of PolyOmica, a private genomics research organization; these relationships do not pose known conflicts with the content of this work presented. We the authors do not have any other financial interests that could create a potential conflict or the appearance of a potential conflict of interest with regard to this work.

  • All grant/financial support for this work is reported in the acknowledgements section of the manuscript.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.
Back to top
PreviousNext
Posted January 20, 2018.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Genome-wide Meta-analysis of 158,000 Individuals of European Ancestry Identifies Three Loci Associated with Chronic Back Pain
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Genome-wide Meta-analysis of 158,000 Individuals of European Ancestry Identifies Three Loci Associated with Chronic Back Pain
Pradeep Suri, Melody R. Palmer, Yakov A. Tsepilov, Maxim B. Freidin, Cindy G. Boer, Michelle S. Yau, Daniel S. Evans, Andrea Gelemanovic, Traci M. Bartz, Maria Nethander, Liubov Arbeeva, Lennart Karssen, Tuhina Neogi, Archie Campbell, Dan Mellstrom, Claes Ohlsson, Lynn M. Marshall, Eric Orwoll, Andre Uitterlinden, Jerome I. Rotter, Gordan Lauc, Bruce M. Psaty, Magnus K Karlsson, Nancy E. Lane, Gail Jarvik, Ozren Polasek, Marc Hochberg, Joanne M. Jordan, Joyce B. J. Van Meurs, Rebecca Jackson, Carrie M. Nielson, Braxton D. Mitchell, Blair H. Smith, Caroline Hayward, Nicholas L. Smith, Yurii S. Aulchenko, Frances M.K. Williams
bioRxiv 244483; doi: https://doi.org/10.1101/244483
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Genome-wide Meta-analysis of 158,000 Individuals of European Ancestry Identifies Three Loci Associated with Chronic Back Pain
Pradeep Suri, Melody R. Palmer, Yakov A. Tsepilov, Maxim B. Freidin, Cindy G. Boer, Michelle S. Yau, Daniel S. Evans, Andrea Gelemanovic, Traci M. Bartz, Maria Nethander, Liubov Arbeeva, Lennart Karssen, Tuhina Neogi, Archie Campbell, Dan Mellstrom, Claes Ohlsson, Lynn M. Marshall, Eric Orwoll, Andre Uitterlinden, Jerome I. Rotter, Gordan Lauc, Bruce M. Psaty, Magnus K Karlsson, Nancy E. Lane, Gail Jarvik, Ozren Polasek, Marc Hochberg, Joanne M. Jordan, Joyce B. J. Van Meurs, Rebecca Jackson, Carrie M. Nielson, Braxton D. Mitchell, Blair H. Smith, Caroline Hayward, Nicholas L. Smith, Yurii S. Aulchenko, Frances M.K. Williams
bioRxiv 244483; doi: https://doi.org/10.1101/244483

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Genomics
Subject Areas
All Articles
  • Animal Behavior and Cognition (2516)
  • Biochemistry (4961)
  • Bioengineering (3462)
  • Bioinformatics (15165)
  • Biophysics (6878)
  • Cancer Biology (5374)
  • Cell Biology (7699)
  • Clinical Trials (138)
  • Developmental Biology (4514)
  • Ecology (7127)
  • Epidemiology (2059)
  • Evolutionary Biology (10204)
  • Genetics (7495)
  • Genomics (9762)
  • Immunology (4815)
  • Microbiology (13167)
  • Molecular Biology (5124)
  • Neuroscience (29342)
  • Paleontology (203)
  • Pathology (834)
  • Pharmacology and Toxicology (1460)
  • Physiology (2126)
  • Plant Biology (4728)
  • Scientific Communication and Education (1008)
  • Synthetic Biology (1337)
  • Systems Biology (4001)
  • Zoology (768)