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 & 17 others Gordan Lauc, Bruce M. Psaty, Magnus K. Karlsson, 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

Research output: Contribution to journalArticle

4 Citations (Scopus)

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).

Original languageEnglish (US)
Article numbere1007601
JournalPLoS Genetics
Volume14
Issue number9
DOIs
StatePublished - Sep 1 2018

Fingerprint

back (body region)
meta-analysis
Back Pain
ancestry
Chronic Pain
Meta-Analysis
pain
genome
Genome
loci
Genome-Wide Association Study
Joints
Logistic Models
disability-adjusted life year
sampling
Genetic Loci
genotyping
signs and symptoms (animals and humans)
epidemiology
disability

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Cite this

Suri, P., Palmer, M. R., Tsepilov, Y. A., Freidin, M. B., Boer, C. G., Yau, M. S., ... Williams, F. M. K. (2018). Genome-wide meta-analysis of 158,000 individuals of European ancestry identifies three loci associated with chronic back pain. PLoS Genetics, 14(9), [e1007601]. https://doi.org/10.1371/journal.pgen.1007601

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.; Nethander, Maria; Arbeeva, Liubov; Karssen, Lennart; Neogi, Tuhina; Campbell, Archie; Mellstrom, Dan; Ohlsson, Claes; Marshall, Lynn M.; Orwoll, Eric; Uitterlinden, Andre; Rotter, Jerome I.; Lauc, Gordan; Psaty, Bruce M.; Karlsson, Magnus K.; Lane, Nancy E; Jarvik, Gail P.; Polasek, Ozren; Hochberg, Marc; Jordan, Joanne M.; Van Meurs, Joyce B.J.; Jackson, Rebecca; Nielson, Carrie M.; Mitchell, Braxton D.; Smith, Blair H.; Hayward, Caroline; Smith, Nicholas L.; Aulchenko, Yurii S.; Williams, Frances M.K.

In: PLoS Genetics, Vol. 14, No. 9, e1007601, 01.09.2018.

Research output: Contribution to journalArticle

Suri, P, Palmer, MR, Tsepilov, YA, Freidin, MB, Boer, CG, Yau, MS, Evans, DS, Gelemanovic, A, Bartz, TM, Nethander, M, Arbeeva, L, Karssen, L, Neogi, T, Campbell, A, Mellstrom, D, Ohlsson, C, Marshall, LM, Orwoll, E, Uitterlinden, A, Rotter, JI, Lauc, G, Psaty, BM, Karlsson, MK, Lane, NE, Jarvik, GP, Polasek, O, Hochberg, M, Jordan, JM, Van Meurs, JBJ, Jackson, R, Nielson, CM, Mitchell, BD, Smith, BH, Hayward, C, Smith, NL, Aulchenko, YS & Williams, FMK 2018, 'Genome-wide meta-analysis of 158,000 individuals of European ancestry identifies three loci associated with chronic back pain', PLoS Genetics, vol. 14, no. 9, e1007601. https://doi.org/10.1371/journal.pgen.1007601
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. ; Nethander, Maria ; Arbeeva, Liubov ; Karssen, Lennart ; Neogi, Tuhina ; Campbell, Archie ; Mellstrom, Dan ; Ohlsson, Claes ; Marshall, Lynn M. ; Orwoll, Eric ; Uitterlinden, Andre ; Rotter, Jerome I. ; Lauc, Gordan ; Psaty, Bruce M. ; Karlsson, Magnus K. ; Lane, Nancy E ; Jarvik, Gail P. ; Polasek, Ozren ; Hochberg, Marc ; Jordan, Joanne M. ; Van Meurs, Joyce B.J. ; Jackson, Rebecca ; Nielson, Carrie M. ; Mitchell, Braxton D. ; Smith, Blair H. ; Hayward, Caroline ; Smith, Nicholas L. ; Aulchenko, Yurii S. ; Williams, Frances M.K. / Genome-wide meta-analysis of 158,000 individuals of European ancestry identifies three loci associated with chronic back pain. In: PLoS Genetics. 2018 ; Vol. 14, No. 9.
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T1 - Genome-wide meta-analysis of 158,000 individuals of European ancestry identifies three loci associated with chronic back pain

AU - Suri, Pradeep

AU - Palmer, Melody R.

AU - Tsepilov, Yakov A.

AU - Freidin, Maxim B.

AU - Boer, Cindy G.

AU - Yau, Michelle S.

AU - Evans, Daniel S.

AU - Gelemanovic, Andrea

AU - Bartz, Traci M.

AU - Nethander, Maria

AU - Arbeeva, Liubov

AU - Karssen, Lennart

AU - Neogi, Tuhina

AU - Campbell, Archie

AU - Mellstrom, Dan

AU - Ohlsson, Claes

AU - Marshall, Lynn M.

AU - Orwoll, Eric

AU - Uitterlinden, Andre

AU - Rotter, Jerome I.

AU - Lauc, Gordan

AU - Psaty, Bruce M.

AU - Karlsson, Magnus K.

AU - Lane, Nancy E

AU - Jarvik, Gail P.

AU - Polasek, Ozren

AU - Hochberg, Marc

AU - Jordan, Joanne M.

AU - Van Meurs, Joyce B.J.

AU - Jackson, Rebecca

AU - Nielson, Carrie M.

AU - Mitchell, Braxton D.

AU - Smith, Blair H.

AU - Hayward, Caroline

AU - Smith, Nicholas L.

AU - Aulchenko, Yurii S.

AU - Williams, Frances M.K.

PY - 2018/9/1

Y1 - 2018/9/1

N2 - 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).

AB - 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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