Genome-wide meta-analysis of 158,000 individuals of European ancestry identifies three loci associated with chronic back pain
Year: 2024
Type: review
Study design: Observational Study
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).
DOI: 10.17615/36rr-ma25
Authors: Rotter, Jerome I., Smith, Blair H., Karlsson, Magnus K., Yau, Michelle S., Williams, Frances M. K., Bartz, Traci M., Smith, Nicholas L., Nethander, Maria, Freidin, Maxim B., Karssen, Lennart, Marshall, Lynn M., Evans, Daniel S., Polasek, Ozren, Mitchell, Braxton D., Jordan, Joanne M., Jackson, Rebecca, Hayward, Caroline, Van Meurs, Joyce B. J., Hochberg, Marc, Suri, Pradeep, Gelemanovic, Andrea, Psaty, Bruce M., Lane, Nancy E., Boer, Cindy G., Campbell, Archie, Palmer, Melody R., Jarvik, Gail P., Uitterlinden, Andre, Nielson, Carrie M., Ohlsson, Claes, Orwoll, Eric, Arbeeva, Liubov, Lauc, Gordan, Mellstrom, Dan, Neogi, Tuhina, Aulchenko, Yurii S., Tsepilov, Yakov A.
Institution: University of North Carolina at Chapel Hill
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funders: U.S. Department of Veterans Affairs, Women's Health Initiative, Association of Schools and Programs of Public Health, School of Medicine, Boston University, Wellcome Trust, Scottish Government, National Institute for Health and Care Research, Novo Nordisk UK Research Foundation, Scottish Funding Council, King's College London, European Commission, Stiftelsen för Strategisk Forskning, ZonMw, Erasmus Medisch Centrum, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Ministry of Education and Science of the Russian Federation, Knut och Alice Wallenbergs Stiftelse, Novo Nordisk, Vetenskapsrådet, Hrvatska Zaklada za Znanost, Novo Nordisk Fonden, National Institutes of Health, Centers for Disease Control and Prevention, Chief Scientist Office, Scottish Government Health and Social Care Directorate, Medical Research Council, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Institute of Environmental Health Sciences, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Center for Research Resources, National Center for Chronic Disease Prevention and Health Promotion, National Center for Advancing Translational Sciences, Army Research Office
Awards: G1023702118, G1028935811, G1097528416, G1158108047, G125972088, G1360395589, G1385097769, G1397335784, G1401438683, Osteoporotic Fractures in Men (MrOS) - Minneapolis, G1438302022, G166592988, G1726490033, G1753550067, Osteoporotic Fractures in Men, Oregon Clinical and Translational Research Institute, Genome-wide case-only study of antihypertensive drug-gene interactions, Osteoporatic Fractures in Men (MrOS), G232264632, G2399901895, G2429472340, G2437620908, G250621538, Multi-dimensional omics approach to stratification of patients with low back pain, G270907595, G2791092843, G2791745117, G2800149121, G2918387404, G2929263391, WGA Study to Identify Genetic Variants Associated with CV Events in CHS, G3049869442, G308144979, G3137375862, Prospective meta-analyses of drug-gene interactions: CHARGE GWAS consortium, G3205625555, G3220743633, G322252321, G3265480162, UCLA Clinical and Translational Science Institute, G3396628412, G34347772, G3478446248, G3531780063, Osteoporotic Fractures in Men (Mr. Os) Palo Alto, G3692229207, G36937976, Osteoporotic Fractures in Men - MrOS Renewal, G400178218, Osteoporotic Fractures in Men, G409491633, G412671775, G4219624527, G4228804694, G423252844, G4234090350, G4253755194, Osteoporotic Fractures in Men - MrOS Renewal - Birmingham, Osteoporotic Fractures in Men - MrOS Renewal - Pittsburgh, Osteoporotic Fractures in Men (MrOS) - Administrative Center, G4567576954, G4622379297, G462704701, G4710253500, G4712859843, G482432850, G4942589162, Osteoporosis in Men, G500195777, G5145575165, G5206110354, G5251985303, G5281659474, G5281952516, G544148272, G5479317095, G5672476635, CHARGE consortium: omics discovery for CVD and aging phenotypes, CHS Events Follow-up Study, Osteoporotic Fractures in Men (MrOS) Renewal - Portland, G604760239, Oregon Clinical and Translational Research Institute, G659721583, G65980962, Osteoporotic Fractures in Men (Mr.OS), G6731263221, Osteoporotic Fractures in Men (MrOS) - San Francisco Coordinating Center, Mid-Atlantic Nutrition Obesity Research Center, G6986132784, Osteoporotic Fractures in Men (MrOS) - Portland, G7007046788, G7058527481, G7217924807, G724008290, G7333126394, G7446983892, G7505613430, Osteoporotic Fractures in Men_MrOS Renewal_Birmingham, G7571789982, G7637400127, G764651519, G7660759926, G766700449, G766843672, Exceptional Survival: Trajectories to Functional Aging (CHS All Stars), G7775568892, MULTIPURPOSE ARTHRITIS &MUSCULOSKELETAL DISEASES CENTER, G7885066867, G80149192, G806768229, G8068269535, G8125002010, G8260701975, G8384987212, G839044655, G8511401681, G85598970, CHS-Transition Phase -268055222, G8716920314, G8724570043, Epidemiology of Dementia in the Framingham Study, G8860021431, G8892155751, G897039181, G9000001730, G9000027259, G9000033828, G9000046001, G9000069887, G9000124008, G9000124674, G9000125773, G9000139054, G9000140433, G9000155215, G905887895, G930580543, G992156627
OpenAlex ID: W4400699133