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

Suri, Pradeep ; Palmer, Melody R. ; Tsepilov, Yakov A. ; Freidin, Maxim B. ; Boer, Cindy G. ; Yau, Michelle S. ; Evans, Daniel S. ; Gelemanovic, Andrea ; Bartz, Traci M. and Nethander, Maria , et al. (2018) In PLoS Genetics 14(9).
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,... (More)

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).

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publication status
published
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PLoS Genetics
volume
14
issue
9
article number
e1007601
publisher
Public Library of Science (PLoS)
external identifiers
  • pmid:30261039
  • scopus:85054564552
ISSN
1553-7390
DOI
10.1371/journal.pgen.1007601
language
English
LU publication?
yes
id
9215acb0-69f2-4bbf-be05-7f4b9bf1794f
date added to LUP
2018-11-05 14:00:21
date last changed
2024-04-15 15:40:25
@article{9215acb0-69f2-4bbf-be05-7f4b9bf1794f,
  abstract     = {{<p>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&lt;5×10<sup>−8</sup>. Suggestive (p&lt;5×10<sup>−7</sup>) and genome-wide significant (p&lt;5×10<sup>−8</sup>) 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<sup>−10</sup>). 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<sup>−11</sup>), and exceeded genome-wide significance in joint meta-analysis (OR 1.07, p = 4.5×10<sup>−19</sup>). 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<sup>−13</sup>), and an intronic variant, rs4384683, in DCC (OR 0.97, p = 2.4×10<sup>−10</sup>). 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).</p>}},
  author       = {{Suri, Pradeep and Palmer, Melody R. and Tsepilov, Yakov A. and Freidin, Maxim B. and Boer, Cindy G. and Yau, Michelle S. and Evans, Daniel S. and Gelemanovic, Andrea and Bartz, Traci M. and Nethander, Maria and Arbeeva, Liubov and Karssen, Lennart and Neogi, Tuhina and Campbell, Archie and Mellstrom, Dan and Ohlsson, Claes and Marshall, Lynn M. and Orwoll, Eric and Uitterlinden, Andre and Rotter, Jerome I. and Lauc, Gordan and Psaty, Bruce M. and Karlsson, Magnus K. and Lane, Nancy E. and Jarvik, Gail P. and Polasek, Ozren and Hochberg, Marc and Jordan, Joanne M. and Van Meurs, Joyce B.J. and Jackson, Rebecca and Nielson, Carrie M. and Mitchell, Braxton D. and Smith, Blair H. and Hayward, Caroline and Smith, Nicholas L. and Aulchenko, Yurii S. and Williams, Frances M.K.}},
  issn         = {{1553-7390}},
  language     = {{eng}},
  number       = {{9}},
  publisher    = {{Public Library of Science (PLoS)}},
  series       = {{PLoS Genetics}},
  title        = {{Genome-wide meta-analysis of 158,000 individuals of European ancestry identifies three loci associated with chronic back pain}},
  url          = {{http://dx.doi.org/10.1371/journal.pgen.1007601}},
  doi          = {{10.1371/journal.pgen.1007601}},
  volume       = {{14}},
  year         = {{2018}},
}