Genome-wide meta-analysis of 158,000 individuals of European ancestry identifies three loci associated with chronic back pain

Research output: Contribution to journalArticle

Abstract

Back pain is the #1 cause of years lived with disability worldwide, yet surprisingly little is known regarding the biology underlying this symptom. We conducted a genome-wide association study (GWAS) meta-analysis of chronic back pain (CBP). Adults of European ancestry were included from 15 cohorts in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and from the UK Biobank interim data release. 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 the remaining UK Biobank participants not included in the discovery sample. The discovery sample comprised 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 283,752 UK Biobank participants not included in the discovery sample, 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). 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).

Details

Authors
  • 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
  • Nancy E. Lane
  • Gail P. 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
Organisations
External organisations
  • U.S. Department of Veterans Affairs
  • VA Puget Sound Health Care System
  • University of Washington
  • King's College London
  • Erasmus University Medical Center
  • Hebrew SeniorLife
  • California Pacific Medical Center
  • University of Split
  • University of Gothenburg
  • Boston University
  • University of Edinburgh
  • Oregon Health & Science University
  • University of California, Los Angeles
  • Kaiser Permanente Research Institute
  • Skåne University Hospital
  • University of California, Davis
  • University of Maryland, Baltimore
  • Ohio State University
  • Veterans Health Administration
  • Novosibirsk State University
  • Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences
  • Beth Israel Deaconess Medical Center
  • Harvard University
  • University of North Carolina
  • PolyOmica
  • Harbor–UCLA Medical Center
  • University of Zagreb
  • Genos d.o.o
  • Psychiatric Hospital "Sveti Ivan"
  • University of Dundee
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics
  • Orthopedics
Original languageEnglish
Article numbere1007601
JournalPLoS Genetics
Volume14
Issue number9
Publication statusPublished - 2018
Publication categoryResearch
Peer-reviewedYes