Genome-wide meta-analysis of 158,000 individuals of European ancestry identifies three loci associated with chronic back pain
Year: 2018
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).
Source: PLoS Genetics
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, Magnus K Karlsson, Nancy E. Lane, Gail 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
Institutions: University of Washington, VA Office of Research and Development, VA Puget Sound Health Care System, Seattle Epidemiologic Information and Research Center, Novosibirsk State University, Institute of Cytology and Genetics, King's College London, Erasmus MC, Beth Israel Deaconess Medical Center, Harvard University, Hebrew SeniorLife, California Pacific Medical Center, University of Split, University of Gothenburg, University of North Carolina at Chapel Hill, Boston University, Institute of Genetics and Cancer, University of Edinburgh, Oregon Health & Science University, University of California, Los Angeles, The Lundquist Institute, Harbor–UCLA Medical Center, University of Zagreb, Genos (Croatia), Kaiser Permanente Washington Health Research Institute, Lund University, Skåne University Hospital, University of California Davis Medical Center, University of California, Davis, Psychiatric Hospital Sveti Ivan, University of Maryland, Baltimore, The Ohio State University, Baltimore VA Medical Center, University of Dundee, MRC Human Genetics Unit
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,043
Funders: U.S. Department of Veterans Affairs, Yale University, School of Medicine, Boston University, Wellcome Trust, Scottish Government, Novo Nordisk UK Research Foundation, Scottish Funding Council, King's College London, European Commission, Stiftelsen för Strategisk Forskning, ZonMw, Erasmus Universiteit Rotterdam, Erasmus Medisch Centrum, Ministerie van Onderwijs, Cultuur en Wetenschap, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, 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, Menzies Centre for Australian Studies, King's College London, University of London, 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 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, G1068966504, G1097528416, G1158108047, G1170704527, G1220223050, G125972088, CORONARY HEART DISEASE AND STROKE, CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84, G130287077, G1343274610, G1352229255, G1360395589, G138000085, G1385097769, G1397335784, Study of Osteoporotic Fractures, G1401438683, Osteoporotic Fractures in Men (MrOS) - Minneapolis, G1438302022, G1490530680, G1493513681, G159340412, CORONARY HEART DISEASE AND STROKE, G1613471689, G166592988, G1711508895, G1726490033, G1753550067, G1880845011, G1922810624, Osteoporotic Fractures in Men, Central Sensitization in Post-Knee Replacement Pain and Relation to OA Pathology, Oregon Clinical and Translational Research Institute, Study of Osteoporotic Fractures, Genome-wide case-only study of antihypertensive drug-gene interactions, Osteoporatic Fractures in Men (MrOS), The Role of Urate in Knee Osteoarthritis-Related Inflammation, Pathology and Pain, Rare variants and NHLBI traits in deeply phenotyped cohorts, G2194386449, Genome-wide Association Study to Identify Genetic Components of Knee OA: The OAI, CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84, G232264632, G2391884931, G2399901895, G2404385439, G2429472340, G2437620908, G245238184, G250621538, G2576967755, G2607611709, CORONARY HEART DISEASE &STROKE IN THE ELDERLY, Multi-dimensional omics approach to stratification of patients with low back pain, G270907595, G2736147164, G2791092843, G2791745117, G2800149121, G2837778307, G2899267414, G2918387404, G2929263391, G3045517347, WGA Study to Identify Genetic Variants Associated with CV Events in CHS, G3049017749, G3049869442, G308144979, G3137375862, Prospective meta-analyses of drug-gene interactions: CHARGE GWAS consortium, G3167614921, G3205625555, G321186775, G3220743633, G322252321, G3265480162, UCLA Clinical and Translational Science Institute, G328531112, G3364068379, G3396628412, G34347772, G3456881708, G3478446248, CHS research resources for the cardiovascular health of older adults, G3531780063, Osteoporotic Fractures in Men (Mr. Os) Palo Alto, G3664726445, G3667269547, G3682927731, G3692229207, G36937976, GWAS in MrOS and SOF, G3918129666, Osteoporotic Fractures in Men - 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Portland, G604760239, G6105757648, G612830406, G6226795708, Stratifying Resilience and Depression Longitudinally (STRADL), MRI, Genetics & Cognitive Precursors of AD and Dementia, The Framingham Heart Study, Oregon Clinical and Translational Research Institute, G659721583, G65980962, Osteoporotic Fractures in Men (Mr.OS), G6706757010, G6731263221, Osteoporotic Fractures in Men (MrOS) - San Francisco Coordinating Center, NIAMS Multidisciplinary Clin Res Ctr: Rheumatic Diseases, G682487154, Study of Osteoporotic Fractures, G6879233014, Mid-Atlantic Nutrition Obesity Research Center, G6986132784, Osteoporotic Fractures in Men (MrOS) - Portland, G7004081433, G7007046788, G7058527481, G7078612884, G7176672723, G7200248429, G7217924807, G724008290, G7244861316, NIAMS Multidisciplinary Clinical Research Center, G7304791810, G7333126394, G7415749889, G7446983892, G7505613430, Osteoporotic Fractures in Men_MrOS Renewal_Birmingham, G7571789982, G7589654153, G7637400127, G764651519, G7660759926, G766700449, G766843672, Exceptional Survival: Trajectories to Functional Aging (CHS All Stars), G7775568892, G778393479, MULTIPURPOSE ARTHRITIS &MUSCULOSKELETAL DISEASES CENTER, G7885066867, G80149192, G806768229, G8068269535, G8125002010, G8151528796, G8260701975, G8330560607, G8333059547, G8384987212, G839044655, G8492638969, G8511401681, G8541424066, G854822065, G85598970, CHS-Transition Phase -268055222, 4 of 4: Study of Osteoporotic Fractures (SOF), G8716920314, G8724570043, G8748734468, Epidemiology of Dementia in the Framingham Study, G8781403166, G8860021431, G8892155751, G897039181, G9000001730, G9000012074, G9000027259, G9000033571, G9000033828, G9000046001, G9000066146, G9000069887, G9000111449, G9000124008, G9000124674, G9000125773, G9000139054, G9000140433, G9000155215, G9000160606, G9000194162, G9000283869, G9000324732, Oregon Clinical and Translational Research Institute, Diabetes Research Center (DRC), Precursors of Stroke Incidence and Prognosis, G905887895, G930580543, G955951203, G961212782, G972017601, G992156627
OpenAlex ID: W2953297691