{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T11:46:15Z","timestamp":1792755975407,"version":"4.5.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,23]],"date-time":"2022-08-23T00:00:00Z","timestamp":1661212800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2022J011457"],"award-info":[{"award-number":["2022J011457"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The association between obesity and musculoskeletal chronic pain has attracted much attention these days; however, the causal relationship between them is uncertain. Hence, this study performed a Mendelian randomization (MR) analysis to investigate the causal effects of body mass index (BMI), waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR) on knee pain, hip pain, and back pain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>The summary data for obesity and musculoskeletal chronic pain came from the genome-wide association study datasets. Significant and independent (<jats:italic>p<\/jats:italic> &amp;lt; 5 \u00d7 10<jats:sup>\u22128<\/jats:sup>; r<jats:sup>2<\/jats:sup> &amp;lt; 0.001, kb = 10,000) single-nucleotide polymorphisms were extracted for MR analysis. The inverse variance weighted (IVW) and other methods were used for MR analysis, while sensitivity analyses were conducted to test the reliability and stability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The positive causal effects of BMI on knee pain (odds ratio (OR) = 1.049; 95% CI: 1.034 to 1.063; <jats:italic>p<\/jats:italic> = 9.88 \u00d7 10<jats:sup>\u221212<\/jats:sup>), hip pain (OR = 1.034; 95% CI: 1.024 to 1.044; <jats:italic>p<\/jats:italic> = 1.38 \u00d7 10<jats:sup>\u221212<\/jats:sup>), and back pain (OR = 1.022; 95% CI: 1.007 to 1.038; <jats:italic>p<\/jats:italic> = 0.004) were observed. WC and HC were also positively associated with knee pain (WC: OR = 1.057; 95% CI: 1.041 to 1.072; <jats:italic>p<\/jats:italic> = 1.54 \u00d7 10<jats:sup>\u221213<\/jats:sup>; HC: OR = 1.034; 95% CI: 1.017 to 1.052; <jats:italic>p<\/jats:italic> = 1.32 \u00d7 10<jats:sup>\u22124<\/jats:sup>) and hip pain (WC: OR = 1.031; 95% CI: 1.020 to 1.042; <jats:italic>p<\/jats:italic> = 2.61 \u00d7 10<jats:sup>\u22128<\/jats:sup>; HC: OR = 1.027; 95% CI: 1.018 to 1.035; <jats:italic>p<\/jats:italic> = 5.48 \u00d7 10<jats:sup>\u221210<\/jats:sup>) but not back pain. No causal relationship was found between WHR and musculoskeletal chronic pain. The results were robust according to sensitivity tests.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study revealed that BMI was positively related to knee, hip, and back pain and that WC and HC were positively associated with knee and hip pain, while WHR was not related to any type of musculoskeletal chronic pain.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2022.971997","type":"journal-article","created":{"date-parts":[[2022,8,23]],"date-time":"2022-08-23T05:06:51Z","timestamp":1661231211000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":24,"title":["Causal relationships of obesity on musculoskeletal chronic pain: A two-sample Mendelian randomization study"],"prefix":"10.3389","volume":"13","author":[{"given":"Xiaoqing","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haifeng","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinding","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongdong","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,8,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"17034","DOI":"10.1038\/nrdp.2017.34","article-title":"Obesity","volume":"3","author":"Gonz\u00e1lez-Muniesa","year":"2017","journal-title":"Nat Rev Dis Primers"},{"key":"B2","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1038\/s41574-019-0201-y","article-title":"Subtyping obesity","volume":"15","author":"Morris","year":"2019","journal-title":"Nat Rev Endocrinol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-020-04579-3","article-title":"Obesity, metabolic syndrome, and primary hypertension","volume":"36","author":"Litwin","year":"2021","journal-title":"Pediatr Nephrol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1186\/s12967-019-2096-8","article-title":"Metabolic signature of obesity-associated insulin resistance and type 2 diabetes","volume":"17","author":"Al-Sulaiti","year":"2019","journal-title":"J Transl Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2019.05.009","article-title":"Gut microbiota and obesity-associated osteoarthritis","volume":"27","author":"Liu","year":"2019","journal-title":"Osteoarthritis Cartilage"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00393-7","article-title":"Chronic pain: An update on burden, best practices, and new advances","volume":"397","author":"Cohen","year":"2021","journal-title":"Lancet"},{"key":"B7","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1001\/jama.2013.13805","article-title":"The state of us health, 1990-2010: Burden of diseases, injuries, and risk factors","volume":"310","author":"Murray","year":"2013","journal-title":"JAMA"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm6736a2","article-title":"Prevalence of chronic pain and high-impact chronic pain among adults - united states, 2016","volume":"67","author":"Dahlhamer","year":"2018","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"B9","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1007\/s13142-012-0110-2","article-title":"The future of pain research, education, and treatment: A summary of the iom report \"Relieving pain in America: A blueprint for transforming prevention, care, education, and research\"","volume":"2","author":"Steglitz","year":"2012","journal-title":"Transl Behav Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3233\/BMR-181384","article-title":"The effect of obesity on pain and disability in chronic shoulder pain patients","volume":"33","author":"Ozkuk","year":"2020","journal-title":"J Back Musculoskelet Rehabil"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.spinee.2015.02.001","article-title":"The relationship between obesity, low back pain, and lumbar disc degeneration when genetics and the environment are considered: A systematic review of twin studies","volume":"15","author":"Dario","year":"2015","journal-title":"Spine J"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ker276","article-title":"The relationship between body mass index across the life course and knee pain in adulthood: Results from the 1958 birth cohort study","volume":"50","author":"Macfarlane","year":"2011","journal-title":"Rheumatol (Oxford)"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1186\/1546-0096-12-11","article-title":"Adolescent obesity, joint pain, and hypermobility","volume":"12","author":"Bout-Tabaku","year":"2014","journal-title":"Pediatr Rheumatol Online J"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.21758","article-title":"Mendelian randomization analysis with multiple genetic variants using summarized data","volume":"37","author":"Burgess","year":"2013","journal-title":"Genet Epidemiol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.k601","article-title":"Reading mendelian randomisation studies: A guide, glossary, and checklist for clinicians","volume":"362","author":"Davies","year":"2018","journal-title":"BMJ"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1002\/sim.3034","article-title":"Mendelian randomization: Using genes as instruments for making causal inferences in epidemiology","volume":"27","author":"Lawlor","year":"2008","journal-title":"Stat Med"},{"key":"B17","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1038\/nature14177","article-title":"Genetic studies of body mass index yield new insights for obesity biology","volume":"518","author":"Locke","year":"2015","journal-title":"Nature"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/nature14132","article-title":"New genetic loci link adipose and insulin biology to body fat distribution","volume":"518","author":"Shungin","year":"2015","journal-title":"Nature"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyx028","article-title":"Two-sample mendelian randomization: Avoiding the downsides of a powerful, widely applicable but potentially fallible technique","volume":"45","author":"Hartwig","year":"2016","journal-title":"Int J Epidemiol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyw220","article-title":"Assessing the suitability of summary data for two-sample mendelian randomization analyses using Mr-egger regression: The role of the I2 statistic","volume":"45","author":"Bowden","year":"2016","journal-title":"Int J Epidemiol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-017-0255-x","article-title":"Interpreting findings from mendelian randomization using the Mr-egger method","volume":"32","author":"Burgess","year":"2017","journal-title":"Eur J Epidemiol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyv080","article-title":"Mendelian randomization with invalid instruments: Effect estimation and bias detection through egger regression","volume":"44","author":"Bowden","year":"2015","journal-title":"Int J Epidemiol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2011.397","article-title":"Obesity and pain are associated in the united states","volume":"20","author":"Stone","year":"2012","journal-title":"Obes (Silver Spring)"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1002\/acr.23710","article-title":"Risk factors for low back pain: A population-based longitudinal study","volume":"71","author":"Shiri","year":"2019","journal-title":"Arthritis Care Res (Hoboken)"},{"key":"B25","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.gerinurse.2020.10.017","article-title":"The association between obesity and chronic pain among community-dwelling older adults: A systematic review and meta-analysis","volume":"42","author":"Qian","year":"2021","journal-title":"Geriatr Nurs"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.archger.2018.01.009","article-title":"Chronic pain and its association with obesity among older adults in China","volume":"76","author":"Li","year":"2018","journal-title":"Arch Gerontol Geriatr"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1002\/eat.23484","article-title":"Pain, eating behavior, and weight outcomes in adolescent girls","volume":"54","author":"Goldschmidt","year":"2021","journal-title":"Int J Eat Disord"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1111\/joor.12771","article-title":"Obesity, sedentarism and tmd-pain in adolescents","volume":"46","author":"Jordani","year":"2019","journal-title":"J Oral Rehabil"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1007\/s00586-015-4055-2","article-title":"Are obesity and body fat distribution associated with low back pain in women? a population-based study of 1128 Spanish twins","volume":"25","author":"Dario","year":"2016","journal-title":"Eur Spine J"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/s41366-019-0505-y","article-title":"Obesity and pain: A systematic review","volume":"44","author":"Chin","year":"2020","journal-title":"Int J Obes (Lond)"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1097\/BRS.0000000000003291","article-title":"Mechanical aspects of intervertebral disc injury and implications on biomechanics","volume":"45","author":"Desmoulin","year":"2020","journal-title":"Spine"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3233\/WOR-141945","article-title":"Severe obesity effect on low back biomechanical stress of manual load lifting","volume":"51","author":"Singh","year":"2015","journal-title":"Work"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20082030","article-title":"Molecular relationships among obesity, inflammation and intervertebra disc degeneration: Are adipokines the common link","volume":"20","author":"Ruiz-Fern\u00e1ndez","year":"2019","journal-title":"Int J Mol Sci"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1007\/s00586-018-5778-7","article-title":"Leptin and the intervertebral disc: A biochemical link exists between obesity, intervertebral disc degeneration and low back pain-an in vitro study in a bovine model","volume":"28","author":"Segar","year":"2019","journal-title":"Eur Spine J"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2013.02.015","article-title":"Galanin receptors possibly modulate the obesity-induced change in pain threshold","volume":"44","author":"Yu","year":"2013","journal-title":"Peptides"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.971997\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,23]],"date-time":"2022-08-23T05:06:54Z","timestamp":1661231214000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.971997\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,23]]},"references-count":35,"alternative-id":["10.3389\/fendo.2022.971997"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2022.971997","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,23]]},"article-number":"971997"}}