{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T07:26:14Z","timestamp":1770967574258,"version":"3.50.1"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T00:00:00Z","timestamp":1747353600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T00:00:00Z","timestamp":1747353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Prog Orthod."],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Observational studies indicate that obesity correlates with jaw development and remodeling; however, causality remains unclear. This study aimed to examine the potential causal relationship between life-course adiposity and jaw anomalies.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Utilizing summary statistics from genome-wide association studies predominantly of European ancestry, we conducted univariable and multivariable Mendelian randomization (MR) to estimate overall and independent effects of six obesity traits (birth weight, childhood body size, childhood body mass index [BMI], adult BMI, adult body fat percentage, and adult waist circumference) on seven jaw anomalies, including bimaxillary hypoplasia, prognathism, retrognathism, and jaw asymmetry. Comprehensive sensitivity analyses verified robustness, assessed heterogeneity, and examined pleiotropy.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>In univariate analyses, genetically predicted thinner childhood body size (inverse variance weighted [IVW] OR: 0.41, 95% CI: 0.27\u20130.62, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), adult BMI (IVW OR: 0.65, 95% CI: 0.53\u20130.80, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), and waist circumference (IVW OR: 0.60, 95% CI: 0.45\u20130.82, <jats:italic>p<\/jats:italic>\u2009=\u20090.001) were significantly associated with the risk of mandibular retrognathia following Bonferroni correction. Multivariable MR analysis revealed a direct causal effect of childhood body size on mandibular retrognathia, independent of birth weight, adult adiposity, growth hormones, and lifestyle factors. No evidence was found for causal associations between life-course adiposity and other jaw anomalies. Sensitivity analyses produced broadly consistent findings.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>This MR study provides new evidence on the direct causal effects of thin childhood body size on the risk of mandibular retrognathia, emphasizing the critical role of early childhood nutrition and weight management in craniofacial development.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s40510-025-00565-3","type":"journal-article","created":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T10:36:50Z","timestamp":1747391810000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Evaluating the causal effects of life-course adiposity on jaw anomalies"],"prefix":"10.1186","volume":"26","author":[{"given":"Xin","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zheng","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qianyi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yubin","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qianglin","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,5,16]]},"reference":[{"key":"565_CR1","doi-asserted-by":"crossref","unstructured":"1. Lobstein T, Jackson-Leach R, Moodie ML, Hall KD, Gortmaker SL, Swinburn BA, et al. Child and adolescent obesity: part of a bigger picture. Lancet (London, England). 2015;385(9986):2510-20.","DOI":"10.1016\/S0140-6736(14)61746-3"},{"key":"565_CR2","doi-asserted-by":"crossref","unstructured":"2. Boutari C, Mantzoros CS. A 2022 update on the epidemiology of obesity and a call to action: as its twin COVID-19 pandemic appears to be receding, the obesity and dysmetabolism pandemic continues to rage on. Metabol Clin Exp. 2022;133:155217.","DOI":"10.1016\/j.metabol.2022.155217"},{"key":"565_CR3","doi-asserted-by":"crossref","unstructured":"3. Afshin A, Forouzanfar MH, Reitsma MB, Sur P, Estep K, Lee A, et al. Health effects of overweight and obesity in 195 countries over 25 years. N Engl J Med. 2017;377(1):13\u201327.","DOI":"10.1056\/NEJMoa1614362"},{"key":"565_CR4","doi-asserted-by":"crossref","unstructured":"4. Chen X, Cheng Z, Xu J, Wang Q, Zhao Z, Jiang Q. Causal effects of life course adiposity on temporomandibular disorders: A Mendelian randomization study. J Oral Rehabil. 2024;51(2):278\u2009\u2212\u200986.","DOI":"10.1111\/joor.13607"},{"key":"565_CR5","doi-asserted-by":"crossref","unstructured":"5. Vora SR, Tam S, Katsube M, Pliska B, Heda K. Craniofacial form differences between obese and nonobese children. Am J Orthod Den Orthop. 2022;162(5):744\u201352.e3.","DOI":"10.1016\/j.ajodo.2021.07.018"},{"key":"565_CR6","doi-asserted-by":"crossref","unstructured":"6. Hancock S, Carmack A, Kocher M, Rezende Silva E, Sulkowski T, Nanney E, et al. Influence of BMI percentile on craniofacial morphology and development in adolescents,Part II: elevated BMI is associated with larger final facial dimensions. Eur J Orthod. 2024;46(1).","DOI":"10.1093\/ejo\/cjad043"},{"key":"565_CR7","doi-asserted-by":"crossref","unstructured":"7. Sadeghianrizi A, Forsberg CM, Marcus C, Dahll\u00f6f G. Craniofacial development in obese adolescents. Eur J Orthod. 2005;27(6):550-5.","DOI":"10.1093\/ejo\/cji048"},{"key":"565_CR8","doi-asserted-by":"crossref","unstructured":"8. Yagasaki Y, Yamaguchi T, Watahiki J, Konishi M, Katoh H, Maki K. The role of craniofacial growth in leptin deficient (ob\/ob) mice. Orthod Craniof Res. 2003;6(4):233\u221241.","DOI":"10.1034\/j.1600-0544.2003.00260.x"},{"key":"565_CR9","doi-asserted-by":"crossref","unstructured":"9. Takaoka R, Kuyama K, Yatani H, Ishigaki S, Kayashima H, Koishi Y, et al. Involvement of an FTO gene polymorphism in the temporomandibular joint osteoarthritis. Clin Oral Investig. 2022;26(3):2965-73.","DOI":"10.1007\/s00784-021-04278-9"},{"key":"565_CR10","doi-asserted-by":"crossref","unstructured":"10. Danze A, Jacox LA, Bocklage C, Whitley J, Moss K, Hardigan P, et al. Influence of BMI percentile on craniofacial morphology and development in children and adolescents. Eur J Orthod. 2021;43(2):184\u221292.","DOI":"10.1093\/ejo\/cjaa056"},{"key":"565_CR11","doi-asserted-by":"crossref","unstructured":"11. Sischo L, Wilson-Genderson M, Broder HL. Quality-of-life in children with orofacial clefts and caregiver well-being. J Dent Res. 2017;96(13):1474-81.","DOI":"10.1177\/0022034517725707"},{"key":"565_CR12","doi-asserted-by":"crossref","unstructured":"12. He D, Cheng S, Wei W, Zhao Y, Cai Q, Chu X, et al. Body shape from birth to adulthood is associated with skeletal development: a Mendelian randomization study. Bone. 2024;187:117191.","DOI":"10.1016\/j.bone.2024.117191"},{"key":"565_CR13","doi-asserted-by":"crossref","unstructured":"13. Power GM, Tobias JH, Frayling TM, Tyrrell J, Hartley AE, Heron JE, et al. Age-specific effects of weight-based body size on fracture risk in later life: a lifecourse Mendelian randomisation study. Eur J Epidemiol. 2023;38(7):795\u2013807.","DOI":"10.1007\/s10654-023-00986-6"},{"key":"565_CR14","unstructured":"14. Kurki MI, Karjalainen J, Palta P, Sipil\u00e4 TP, Kristiansson K, Donner KM, et al. FinnGen provides genetic insights from a well-phenotyped isolated population. Nature. 2023;613(7944):508\u221218."},{"key":"565_CR15","doi-asserted-by":"crossref","unstructured":"15. Al-Taai N, Persson M, Ransj\u00f6 M, Levring J\u00e4ghagen E, Fors R, Westerlund A. Craniofacial changes from 13 to 62 years of age. Eur J Orthod. 2022;44(5):556\u221265.","DOI":"10.1093\/ejo\/cjac011"},{"key":"565_CR16","doi-asserted-by":"crossref","unstructured":"16. V\u00f6lgyi E, Tylavsky FA, Xu L, Lu J, Wang Q, Al\u00e9n M, et al. Bone and body segment lengthening and widening: a 7-year follow-up study in pubertal girls. Bone. 2010;47(4):773\u221282.","DOI":"10.1016\/j.bone.2010.07.007"},{"key":"565_CR17","doi-asserted-by":"crossref","unstructured":"17. Richardson TG, Sanderson E, Elsworth B, Tilling K, Davey Smith G. Use of genetic variation to separate the effects of early and later life adiposity on disease risk: mendelian randomisation study. BMJ (Clinical research ed). 2020;369:m1203.","DOI":"10.1136\/bmj.m1203"},{"key":"565_CR18","doi-asserted-by":"crossref","unstructured":"18. Loh PR, Kichaev G, Gazal S, Schoech AP, Price AL. Mixed-model association for biobank-scale datasets. Nat Genet. 2018;50(7):906-8.","DOI":"10.1038\/s41588-018-0144-6"},{"key":"565_CR19","unstructured":"19. Vogelezang S, Bradfield JP, Ahluwalia TS, Curtin JA, Lakka TA, Grarup N, et al. Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits. PLoS Genet. 2020;16(10):e1008718."},{"key":"565_CR20","doi-asserted-by":"crossref","unstructured":"20. Xiao P, Li C, Mi J, Wu J. Evaluating the distinct effects of body mass index at childhood and adulthood on adult major psychiatric disorders. Sci Adv. 2024;10(37):eadq2452.","DOI":"10.1126\/sciadv.adq2452"},{"key":"565_CR21","doi-asserted-by":"crossref","unstructured":"21. Chen X, Cheng Z, Xu J, Wang Q, Zhao Z, Jiang Q. Causal effects of autoimmune diseases on temporomandibular disorders and the mediating pathways: a Mendelian randomization study. Front Immunol. 2024;15:1390516.","DOI":"10.3389\/fimmu.2024.1390516"},{"key":"565_CR22","doi-asserted-by":"crossref","unstructured":"22. Verbanck M, Chen CY, Neale B, Do R. Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nat Genet. 2018;50(5):693-8.","DOI":"10.1038\/s41588-018-0099-7"},{"key":"565_CR23","doi-asserted-by":"crossref","unstructured":"23. Bowden J, Davey Smith G, Haycock PC, Burgess S. Consistent estimation in Mendelian randomization with some invalid instruments using a weighted median estimator. Genet Epidemiol. 2016;40(4):304\u221214.","DOI":"10.1002\/gepi.21965"},{"key":"565_CR24","doi-asserted-by":"crossref","unstructured":"24. Grant AJ, Burgess S. Pleiotropy robust methods for multivariable Mendelian randomization. Stat Med. 2021;40(26):5813-30.","DOI":"10.1002\/sim.9156"},{"key":"565_CR25","doi-asserted-by":"crossref","unstructured":"25. Primozic J, Farcnik F, Ovsenik M, Primozic J. A controlled study of the functional and morphological characteristics of malocclusion in prematurely born subjects with low birth weight. Eur J Orthod. 2014;36(1):114\u221220.","DOI":"10.1093\/ejo\/cjt016"},{"key":"565_CR26","doi-asserted-by":"crossref","unstructured":"26. Chen X, Cheng Z, Xu J, Wang Q, Zhao Z, Jiang Q. Causal effects of educational attainment on temporomandibular disorders and the mediating pathways: a Mendelian randomization study. J Oral Rehabil. 2024;51(5):817\u221226.","DOI":"10.1111\/joor.13654"},{"key":"565_CR27","doi-asserted-by":"crossref","unstructured":"27. Rodr\u00edguez-Olivos LHG, Chac\u00f3n-Uscamaita PR, Quinto-Argote AG, Pumahualcca G, P\u00e9rez-Vargas LF. Deleterious oral habits related to vertical, transverse and sagittal dental malocclusion in pediatric patients. BMC Oral Health. 2022;22(1):88.","DOI":"10.1186\/s12903-022-02122-4"},{"key":"565_CR28","doi-asserted-by":"crossref","unstructured":"28. Visnapuu V, Peltom\u00e4ki T, R\u00f6nning O, Vahlberg T, Helenius H. Growth hormone and insulin-like growth factor I receptors in the temporomandibular joint of the rat. J Dent Res. 2001;80(10):1903-7.","DOI":"10.1177\/00220345010800100801"},{"key":"565_CR29","doi-asserted-by":"crossref","unstructured":"29. Hoskins WE, Asling CW. Influence of growth hormone and thyroxine on endochondral osteogenesis in the mandibular condyle and proximal tibial epiphysis. J Dent Res. 1977;56(5):509\u221217.","DOI":"10.1177\/00220345770560051101"},{"key":"565_CR30","doi-asserted-by":"crossref","unstructured":"30. Radalj Mili\u010di\u0107 Z, Kranj\u010devi\u0107 Bubica A, Nikolov Bori\u0107 D, \u0160palj S, Me\u0161trovi\u0107 S. Linear predictors of facial rotation pattern in croatian subjects with skeletal class III Malocclusion. Acta Stomatol Croatica. 2018;52(3):227\u221237.","DOI":"10.15644\/asc52\/3\/6"},{"key":"565_CR31","doi-asserted-by":"crossref","unstructured":"31. Wang X, Yang Y, Lin L, Yao Q, Zhang J. Obesity and temporomandibular joint disorders: a systematic review and meta-analysis. BMC Oral Health. 2023;23(1):607.","DOI":"10.1186\/s12903-023-03322-2"},{"key":"565_CR32","doi-asserted-by":"crossref","unstructured":"32. Stoll ML, Amin D, Powell KK, Poholek CH, Strait RH, Aban I, et al. Risk factors for intraarticular heterotopic bone formation in the temporomandibular joint in juvenile idiopathic arthritis. J Rheumatol. 2018;45(9):1301-7.","DOI":"10.3899\/jrheum.171306"},{"key":"565_CR33","doi-asserted-by":"crossref","unstructured":"33. Inarejos Clemente EJ, Tolend M, Navallas M, Doria AS, Meyers AB. MRI of the temporomandibular joint in children with juvenile idiopathic arthritis: protocol and findings. Pediatr Radiol. 2023;53(8):1498\u2009\u2212\u2009512.","DOI":"10.1007\/s00247-023-05616-7"},{"key":"565_CR34","doi-asserted-by":"crossref","unstructured":"34. Paoli JR, Lauwers F, Lacassagne L, Tiberge M, Dodart L, Boutault F. Craniofacial differences according to the body mass index of patients with obstructive sleep apnoea syndrome: cephalometric study in 85 patients. Br J Oral Maxillofac Surg. 2001;39(1):40\u22125.","DOI":"10.1054\/bjom.2000.0551"},{"key":"565_CR35","doi-asserted-by":"crossref","unstructured":"35. Collins KH, Gui C, Ely EV, Lenz KL, Harris CA, Guilak F, et al. Leptin mediates the regulation of muscle mass and strength by adipose tissue. J Physiol. 2022;600(16):3795\u2212817.","DOI":"10.1113\/JP283034"},{"key":"565_CR36","doi-asserted-by":"crossref","unstructured":"36. Hou HM, H\u00e4gg U, Sam K, Rabie AB, Wong RW, Lam B, et al. Dentofacial characteristics of Chinese obstructive sleep apnea patients in relation to obesity and severity. Angle Orthod. 2006;76(6):962-9.","DOI":"10.2319\/081005-273"},{"key":"565_CR37","doi-asserted-by":"crossref","unstructured":"37. Gosman JH, Stout SD, Larsen CS. Skeletal biology over the life span: a view from the surfaces. Am J Phys Anthropol. 2011;146 Suppl 53:86\u201398.","DOI":"10.1002\/ajpa.21612"},{"key":"565_CR38","doi-asserted-by":"crossref","unstructured":"38. Chia AR, Chen LW, Lai JS, Wong CH, Neelakantan N, van Dam RM, et al. Maternal dietary patterns and birth outcomes: a systematic review and meta-analysis. Adv Nutr (Bethesda, Md). 2019;10(4):685\u221295.","DOI":"10.1093\/advances\/nmy123"},{"key":"565_CR39","doi-asserted-by":"crossref","unstructured":"39. Sandhu J, Ben-Shlomo Y, Cole TJ, Holly J, Davey Smith G. The impact of childhood body mass index on timing of puberty, adult stature and obesity: a follow-up study based on adolescent anthropometry recorded at Christ\u2019s Hospital (1936\u20131964). Int J Obes (2005). 2006;30(1):14\u201322.","DOI":"10.1038\/sj.ijo.0803156"},{"key":"565_CR40","doi-asserted-by":"crossref","unstructured":"40. Huang JS, Becerra K, Walker E, Hovell MF. Childhood overweight and orthodontists: results of a survey. J Public Health Dent. 2006;66(4):292-4.","DOI":"10.1111\/j.1752-7325.2006.tb04087.x"},{"key":"565_CR41","doi-asserted-by":"crossref","unstructured":"41. Norris SA, Frongillo EA, Black MM, Dong Y, Fall C, Lampl M, et al. Nutrition in adolescent growth and development. Lancet (London, England). 2022;399(10320):172\u221284.","DOI":"10.1016\/S0140-6736(21)01590-7"},{"key":"565_CR42","doi-asserted-by":"crossref","unstructured":"42. Sudlow C, Gallacher J, Allen N, Beral V, Burton P, Danesh J, et al. UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med. 2015;12(3):e1001779.","DOI":"10.1371\/journal.pmed.1001779"},{"key":"565_CR43","doi-asserted-by":"crossref","unstructured":"43. Forsum E, Flinke Carlsson E, Henriksson H, Henriksson P, L\u00f6f M. Total body fat content versus BMI in 4-year-old healthy Swedish children. J Obes. 2013;2013:206715.","DOI":"10.1155\/2013\/206715"},{"key":"565_CR44","doi-asserted-by":"crossref","unstructured":"44. Rongo R, Antoun JS, Lim YX, Dias G, Valletta R, Farella M. Three-dimensional evaluation of the relationship between jaw divergence and facial soft tissue dimensions. Angle Orthod. 2014;84(5):788\u221294.","DOI":"10.2319\/092313-699.1"}],"container-title":["Progress in Orthodontics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40510-025-00565-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40510-025-00565-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40510-025-00565-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T10:37:08Z","timestamp":1747391828000},"score":1,"resource":{"primary":{"URL":"https:\/\/progressinorthodontics.springeropen.com\/articles\/10.1186\/s40510-025-00565-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,16]]},"references-count":44,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["565"],"URL":"https:\/\/doi.org\/10.1186\/s40510-025-00565-3","relation":{},"ISSN":["2196-1042"],"issn-type":[{"value":"2196-1042","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,16]]},"assertion":[{"value":"9 November 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 May 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 May 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The present MR study was based on the previously collected and published data, no ethics approval was required.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"18"}}