{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T23:26:04Z","timestamp":1793489164794,"version":"4.5.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,8]],"date-time":"2021-12-08T00:00:00Z","timestamp":1638921600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>The role of obesity in the development of dorsopathies is still unclear. In this study, we assessed the associations between body mass index (BMI) and several dorsopathies including intervertebral disc degeneration (IVDD), low back pain (LBP), and sciatica by using the Mendelian randomization method. We also assessed the effect of several obesity-related traits on the same outcomes. Single-nucleotide polymorphisms associated with the exposures are extracted from summary-level datasets of previously published genome-wide association studies. Summary-level results of IVDD, LBP, and sciatica were from FinnGen. In our univariable Mendelian randomization analysis, BMI is significantly associated with increased risks of all dorsopathies including sciatica (OR = 1.33, 95% CI, 1.21\u20131.47, p = 5.19 \u00d7 10<jats:sup>-9<\/jats:sup>), LBP (OR = 1.28, 95% CI, 1.18\u20131.39, p = 6.60 \u00d7 10<jats:sup>-9<\/jats:sup>), and IVDD (OR = 1.23, 95% CI, 1.14\u20131.32, p = 2.48 \u00d7 10<jats:sup>-8<\/jats:sup>). Waist circumference, hip circumference, whole-body fat mass, fat-free mass, and fat percentage, but not waist\u2013hip ratio, were causally associated with increased risks of IVDD and sciatica. Higher hip circumference, whole-body fat mass, fat-free mass, and fat percentage increased the risk of LBP. However, only whole-body fat-free mass remained to have a significant association with the risk of IVDD after adjusting for BMI with an odds ratio of 1.57 (95% CI, 1.32\u20131.86, p = 2.47 \u00d7 10<jats:sup>-7<\/jats:sup>). Proportions of BMI\u2019s effect on IVDD, sciatica, and LBP mediated by leisure sedentary behavior were 41.4% (95% CI, 21.8%, 64.8%), 33.8% (95% CI, 17.5%, 53.4%), and 49.7% (95% CI, 29.4%, 73.5%), respectively. This study provides evidence that high BMI has causal associations with risks of various dorsopathies. Weight control is a good measure to prevent the development of dorsopathies, especially in the obese population.<\/jats:p>","DOI":"10.3389\/fendo.2021.740200","type":"journal-article","created":{"date-parts":[[2021,12,8]],"date-time":"2021-12-08T04:30:27Z","timestamp":1638937827000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":117,"title":["Causal Associations of Obesity With the Intervertebral Degeneration, Low Back Pain, and Sciatica: A Two-Sample Mendelian Randomization Study"],"prefix":"10.3389","volume":"12","author":[{"given":"Jingzhu","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiarui","family":"Mi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huirong","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengye","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,12,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2017-00111","article-title":"Obesity Pathogenesis: An Endocrine Society Scientific Statement","volume":"38","author":"Schwartz","year":"2017","journal-title":"Endocr Rev"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2004.01.006","article-title":"Recommendations for the Use of New Methods to Assess the Efficacy of Disease-Modifying Drugs in the Treatment of Osteoarthritis","volume":"12","author":"Abadie","year":"2004","journal-title":"Osteoarthritis Cartilage"},{"key":"B3","doi-asserted-by":"publisher","first-page":"e007805","DOI":"10.1136\/bmjopen-2015-007805","article-title":"Role of Overweight and Obesity in Low Back Disorders Among Men: A Longitudinal Study With a Life Course Approach","volume":"5","author":"Frilander","year":"2015","journal-title":"BMJ Open"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1302\/0301-620X.90B10.20910","article-title":"The Pathophysiology of Disc Degeneration: A Critical Review","volume":"90","author":"Hadjipavlou","year":"2008","journal-title":"JTJob Vol jsB"},{"key":"B5","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1111\/j.1533-2500.2007.00171.x","article-title":"Intervertebral Disc: Anatomy-Physiology-Pathophysiology-Treatment","volume":"8","author":"Raj","year":"2008","journal-title":"Pain Pract"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.137836","article-title":"Lumbar Disc Degeneration and Genetic Factors Are the Main Risk Factors for Low Back Pain in Women: The UK Twin Spine Study","volume":"70","author":"Livshits","year":"2011","journal-title":"Ann Rheum Dis"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1002\/art.34347","article-title":"A Systematic Review of the Global Prevalence of Low Back Pain","volume":"64","author":"Hoy","year":"2012","journal-title":"Arthritis Rheum"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1410151","article-title":"Sciatica","volume":"372","author":"Ropper","year":"2015","journal-title":"N Engl J Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.berh.2009.11.005","article-title":"Sciatica","volume":"24","author":"Valat","year":"2010","journal-title":"Best Pract Res Clin Rheumatol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.spinee.2013.08.034","article-title":"Investigating the Role of DNA Damage in Tobacco Smoking-Induced Spine Degeneration","volume":"14","author":"Nasto","year":"2014","journal-title":"Spine J"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1097\/BRS.0000000000001762","article-title":"Biomechanical Evaluation of Transpedicular Nucleotomy With Intact Annulus Fibrosus","volume":"42","author":"Russo","year":"2017","journal-title":"Spine (Phila Pa 1976)"},{"key":"B12","doi-asserted-by":"publisher","first-page":"e3224","DOI":"10.1002\/dmrr.3224","article-title":"Intervertebral Disc Degeneration: A Focus on Obesity and Type 2 Diabetes","volume":"36","author":"Cannata","year":"2020","journal-title":"Diabetes Metab Res Rev"},{"key":"B13","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1111\/j.1469-7580.2012.01551.x","article-title":"Intervertebral Disc Degeneration: Evidence for Two Distinct Phenotypes","volume":"221","author":"Adams","year":"2012","journal-title":"J Anat"},{"key":"B14","doi-asserted-by":"publisher","first-page":"16630","DOI":"10.1038\/s41598-018-34933-3","article-title":"Strong Association Between Vertebral Endplate Defect and Modic Change in the General Population","volume":"8","author":"Maatta","year":"2018","journal-title":"Sci Rep"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1097\/BRS.0000000000002721","article-title":"Endplate Defect Is Heritable, Associated With Low Back Pain and Triggers Intervertebral Disc Degeneration: A Longitudinal Study From TwinsUK","volume":"43","author":"Munir","year":"2018","journal-title":"Spine (Phila Pa 1976)"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1097\/BRS.0000000000002352","article-title":"Vertebral Endplate Defect as Initiating Factor in Intervertebral Disc Degeneration: Strong Association Between Endplate Defect and Disc Degeneration in the General Population","volume":"43","author":"Rade","year":"2018","journal-title":"Spine (Phila Pa 1976)"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1002\/jor.24195","article-title":"Multidimensional Vertebral Endplate Defects Are Associated With Disc Degeneration, Modic Changes, Facet Joint Abnormalities, and Pain","volume":"37","author":"Zehra","year":"2019","journal-title":"J Orthop Res"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijo.0802974","article-title":"Disc Degeneration of the Lumbar Spine in Relation to Overweight","volume":"29","author":"Liuke","year":"2005","journal-title":"Int J Obes (Lond)"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1002\/art.33462","article-title":"The Association of Lumbar Intervertebral Disc Degeneration on Magnetic Resonance Imaging With Body Mass Index in Overweight and Obese Adults: A Population-Based Study","volume":"64","author":"Samartzis","year":"2012","journal-title":"Arthritis Rheum"},{"key":"B20","doi-asserted-by":"publisher","first-page":"e56244","DOI":"10.1371\/journal.pone.0056244","article-title":"Association of Abdominal Obesity With Lumbar Disc Degeneration\u2013a Magnetic Resonance Imaging Study","volume":"8","author":"Takatalo","year":"2013","journal-title":"PloS One"},{"key":"B21","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.spinee.2009.10.005","article-title":"Challenging the Cumulative Injury Model: Positive Effects of Greater Body Mass on Disc Degeneration","volume":"10","author":"Videman","year":"2010","journal-title":"Spine J"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1177\/0962280210394459","article-title":"Using Multiple Genetic Variants as Instrumental Variables for Modifiable Risk Factors","volume":"21","author":"Palmer","year":"2012","journal-title":"Stat Methods Med Res"},{"key":"B23","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":"B24","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu328","article-title":"Mendelian Randomization: Genetic Anchors for Causal Inference in Epidemiological Studies","volume":"23","author":"Davey Smith","year":"2014","journal-title":"Hum Mol Genet"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/ng.685","article-title":"Meta-Analysis Identifies 13 New Loci Associated With Waist-Hip Ratio and Reveals Sexual Dimorphism in the Genetic Basis of Fat Distribution","volume":"42","author":"Heid","year":"2010","journal-title":"Nat Genet"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/ng.686","article-title":"Association Analyses of 249,796 Individuals Reveal 18 New Loci Associated With Body Mass Index","volume":"42","author":"Speliotes","year":"2010","journal-title":"Nat Genet"},{"key":"B27","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":"B28","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":"B29","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":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0099-7","article-title":"Detection of Widespread Horizontal Pleiotropy in Causal Relationships Inferred From Mendelian Randomization Between Complex Traits and Diseases","volume":"50","author":"Verbanck","year":"2018","journal-title":"Nat Genet"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw829","article-title":"The International Genome Sample Resource (IGSR): A Worldwide Collection of Genome Variation Incorporating the 1000 Genomes Project Data","volume":"45","author":"Clarke","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"B32","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1038\/s41467-017-02317-2","article-title":"Causal Associations Between Risk Factors and Common Diseases Inferred From GWAS Summary Data","volume":"9","author":"Zhu","year":"2018","journal-title":"Nat Commun"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyu176","article-title":"Network Mendelian Randomization: Using Genetic Variants as Instrumental Variables to Investigate Mediation in Causal Pathways","volume":"44","author":"Burgess","year":"2015","journal-title":"Int J Epidemiol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.117.300191","article-title":"Dissecting Causal Pathways Using Mendelian Randomization With Summarized Genetic Data: Application to Age at Menarche and Risk of Breast Cancer","volume":"207","author":"Burgess","year":"2017","journal-title":"Genetics"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.34408","article-title":"The MR-Base Platform Supports Systematic Causal Inference Across the Human Phenome","volume":"7","author":"Hemani","year":"2018","journal-title":"Elife"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyy262","article-title":"An Examination of Multivariable Mendelian Randomization in the Single-Sample and Two-Sample Summary Data Settings","volume":"48","author":"Sanderson","year":"2019","journal-title":"Int J Epidemiol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2021.10.005","article-title":"Obesity Could Be Associated With Poor Paraspinal Muscle Quality at Upper Lumbar Levels and Degenerated Spine at Lower Lumbar Levels: Is This a Domino Effect","volume":"94","author":"\u00d6zcan-Ek\u015fi","year":"2021","journal-title":"J\u00a0Clin Neuro"},{"key":"B38","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":"B39","doi-asserted-by":"publisher","DOI":"10.1097\/BSD.0000000000000235","article-title":"Association Between Overweight or Obesity and Lumbar Disk Diseases: A Meta-Analysis","volume":"28","author":"Xu","year":"2015","journal-title":"J Spinal Disord Tech"},{"key":"B40","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":"B41","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":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiomech.2021.110392","article-title":"Increasing BMI Increases Lumbar Intervertebral Disc Deformation Following a Treadmill Walking Stress Test","volume":"121","author":"Coppock","year":"2021","journal-title":"J Biomech"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiomech.2014.11.033","article-title":"Effect of Body Weight on Spinal Loads in Various Activities: A Personalized Biomechanical Modeling Approach","volume":"48","author":"Hajihosseinali","year":"2015","journal-title":"J\u00a0Biomech"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwu007","article-title":"Obesity as a Risk Factor for Sciatica: A Meta-Analysis","volume":"179","author":"Shiri","year":"2014","journal-title":"Am J Epidemiol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1097\/BSD.0000000000000468","article-title":"Obesity as a Risk Factor for Low Back Pain: A Meta-Analysis","volume":"31","author":"Zhang","year":"2018","journal-title":"Clin Spine Surg"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2021.740200\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,8]],"date-time":"2021-12-08T04:30:30Z","timestamp":1638937830000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2021.740200\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,8]]},"references-count":45,"alternative-id":["10.3389\/fendo.2021.740200"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2021.740200","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,8]]},"article-number":"740200"}}