TY - JOUR
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.
N1 - Funding Information:
Infrastructure for the CHARGE Consortium is supported in part by the National Heart, Lung, and Blood Institute grants R01HL105756. This study was supported by the European Commissions’ Seventh Framework Programme funded project PainOmics (Grant agreement n. 602736) Dr. Suri was supported by VA Career Development Award # 1IK2RX001515 from the United States (U.S.) Department of Veterans Affairs Rehabilitation Research and Development (RR&D) Service. Dr. Suri is a Staff Physician at the VA Puget Sound Health Care System. The contents of this work do not represent the views of the U.S. Department of Veterans Affairs or the United States Government. Cardiovascular Health Study: This CHS research was supported by NHLBI contracts HHSN268201200036C, HHSN268200800007C, HHSN268200960009C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086; and NHLBI grants U01HL080295, R01HL087652, R01HL105756, R01HL103612, R01HL120393, R01HL085251, and R01HL130114 with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided through R01AG023629 from the National Institute on Aging (NIA).
Publisher Copyright:
© 2018, Public Library of Science. All rights reserved. https://creativecommons.org/publicdomain/zero/1.0/.
PY - 2018/9
Y1 - 2018/9
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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U2 - 10.1371/journal.pgen.1007601
DO - 10.1371/journal.pgen.1007601
M3 - Article
C2 - 30261039
AN - SCOPUS:85054564552
SN - 1553-7390
VL - 14
JO - PLoS Genetics
JF - PLoS Genetics
IS - 9
M1 - e1007601
ER -