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major cause of disability worldwide. We developed and validated a genome-wide polygenic risk score (PRS) for CBP using a large-scale GWAS based on UK Biobank participants of European ancestry (N = 265,000). The PRS showed poor overall predictive ability (AUC = 0.56 and OR = 1.24 per SD, 95% CI: 1.22\u20131.26), but individuals from the 99th percentile of PRS distribution had a nearly two-fold increased risk of CBP (OR = 1.82, 95% CI: 1.60\u20132.06). We validated the PRS on an independent TwinsUK sample, obtaining a similar magnitude of effect. The PRS was significantly associated with various ICD-10 and OPCS-4 diagnostic codes, including chronic ischemic heart disease (OR = 1.1, p-value = 4.8 \u00d7 10\u221215), obesity, metabolism-related traits, spine disorders, disc degeneration, and arthritis-related disorders. PRS and environment interaction analysis with twelve known CBP risk factors revealed no significant results, suggesting that the magnitude of G \u00d7 E interactions with studied factors is small. The limited predictive ability of the PRS that we developed is likely explained by the complexity, heterogeneity, and polygenicity of CBP, for which sample sizes of a few hundred thousand are insufficient to estimate small genetic effects robustly.<\/jats:p>","DOI":"10.3390\/jpm13060977","type":"journal-article","created":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T03:02:27Z","timestamp":1686538947000},"page":"977","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Development and Replication of a Genome-Wide Polygenic Risk Score for Chronic Back Pain"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4931-6052","authenticated-orcid":false,"given":"Yakov A.","family":"Tsepilov","sequence":"first","affiliation":[{"name":"Laboratory of Recombination and Segregation Analysis, Institute of Cytology and Genetics, Novosibirsk 630090, Russia"},{"name":"Kurchatov Genomics Center, Institute of Cytology and Genetics, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2484-553X","authenticated-orcid":false,"given":"Elizaveta E.","family":"Elgaeva","sequence":"additional","affiliation":[{"name":"Laboratory of Recombination and Segregation Analysis, Institute of Cytology and Genetics, Novosibirsk 630090, Russia"},{"name":"Department of Natural Sciences, Novosibirsk State University, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arina V.","family":"Nostaeva","sequence":"additional","affiliation":[{"name":"Department of Natural Sciences, Novosibirsk State University, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Compte","sequence":"additional","affiliation":[{"name":"Department of Twin Research and Genetic Epidemiology, School of Life Course Sciences, King\u2019s College London, London SE1 7EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4873-0729","authenticated-orcid":false,"given":"Ivan A.","family":"Kuznetsov","sequence":"additional","affiliation":[{"name":"Center of Life Sciences, Skolkovo Institute of Science and Technology, Moscow 121205, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1959-342X","authenticated-orcid":false,"given":"Lennart C.","family":"Karssen","sequence":"additional","affiliation":[{"name":"PolyOmica, 5237 PA s-Hertogenbosch, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1439-6259","authenticated-orcid":false,"given":"Maxim B.","family":"Freidin","sequence":"additional","affiliation":[{"name":"Department of Biology, School of Biological and Behavioural Sciences, Queen Mary University of London, London E1 4NS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradeep","family":"Suri","sequence":"additional","affiliation":[{"name":"Division of Rehabilitation Care Services, VA Puget Sound Health Care System, Seattle, WA 98208, USA"},{"name":"Seattle Epidemiologic Research and Information Center, VA Puget Sound Health Care System, Seattle, WA 98208, USA"},{"name":"Department of Rehabilitation Medicine, University of Washington, Seattle, WA 98208, USA"},{"name":"Clinical Learning, Evidence, and Research (CLEAR) Center, University of Washington, Seattle, WA 98208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2998-2744","authenticated-orcid":false,"given":"Frances M. 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