{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T21:26:38Z","timestamp":1793568398188,"version":"4.5.0"},"reference-count":41,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T00:00:00Z","timestamp":1774656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T00:00:00Z","timestamp":1774656000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Dent Res"],"abstract":"<jats:p>Genetic factors may contribute to the heritability and susceptibility of recurrent aphthous ulcers (RAU). This study evaluated the heritability of RAU in the TwinsUK registry. Data from 890 twin pairs (319 monozygotic [MZ] and 571 dizygotic [DZ]) were used to estimate the prevalence of RAU in the previous year and 8 subphenotypes. A classical twin design was used to partition the variance in RAU presentation into components attributable to additive genetic (A), common\/shared environmental (C), dominance genetic (D), and unique\/nonshared environmental (E) effects. A multilevel ACE\/ADE model with random effects at both the individual and twin-pair levels was fitted to the prevalence of RAU and each subphenotype separately. RAU prevalence in the previous year was 9.3%, with MZ and DZ twin correlations of 0.59 (95% confidence interval [CI]: 0.37, 0.82) and 0.30 (0.09, 0.82), respectively. The ACE model estimated the heritability of RAU prevalence in the previous year at 55.69% (34.43% to 76.95%). Using stricter RAU criteria yielded similar heritability estimates (58.82% [36.51, 81.14]), reinforcing the robustness of the findings. Among subphenotypes, frequency of episodes (53.61% [33.09, 74.13]) and time between occurrences (53.08% [30.96, 75.19]) showed the largest genetic contribution, while ulcer size had the lowest genetic contribution (40.55% [14.76, 66.33]). Heritability estimates for the number of RAU (50.32%, 95% CI: 25.99, 74.65), healing time (49.24% [27.46, 71.03]), and location in soft tissues (42.85% [12.91, 72.78]) and hard tissues (40.70% [12.43, 68.97]) fell between those values. The findings indicate a genetic contribution to RAU susceptibility, with heritability estimates differing across various phenotypic presentations of the condition.<\/jats:p>","DOI":"10.1177\/00220345261431154","type":"journal-article","created":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T09:13:50Z","timestamp":1774689230000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Heritability of Recurrent Aphthous Ulcers: Evidence from a UK Twin Cohort"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5370-2423","authenticated-orcid":false,"given":"A.R.","family":"Tappuni","sequence":"first","affiliation":[{"name":"Institute of Dentistry, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1858-3713","authenticated-orcid":false,"given":"E.","family":"Bernabe","sequence":"additional","affiliation":[{"name":"Institute of Dentistry, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,3,28]]},"reference":[{"key":"e_1_3_2_2_1","doi-asserted-by":"crossref","unstructured":"Akintoye SO Greenberg MS. 2014. Recurrent aphthous stomatitis. Dent Clin North Am. 58(2):281\u2013297. https:\/\/doi.org\/10.1016\/j.cden.2013.12.002","DOI":"10.1016\/j.cden.2013.12.002"},{"key":"e_1_3_2_3_1","doi-asserted-by":"crossref","unstructured":"Baccaglini L Theriaque DW Shuster JJ Serrano G Lalla RV. 2013. Validation of anamnestic diagnostic criteria for recurrent aphthous stomatitis. J Oral Pathol Med. 42(4):290\u2013294. https:\/\/doi.org\/10.1111\/jop.12015","DOI":"10.1111\/jop.12015"},{"key":"e_1_3_2_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajhp\/58.1.41"},{"key":"e_1_3_2_5_1","doi-asserted-by":"crossref","unstructured":"Barry CS et al. 2023. How to estimate heritability: a guide for genetic epidemiologists. Int J Epidemiol. 52(2):624\u2013632. https:\/\/doi.org\/10.1093\/ije\/dyac224","DOI":"10.1093\/ije\/dyac224"},{"key":"e_1_3_2_6_1","doi-asserted-by":"crossref","unstructured":"Bilodeau EA Lalla RV. 2019. Recurrent oral ulceration: etiology classification management and diagnostic algorithm. Periodontol 2000. 80(1):49\u201360. https:\/\/doi.org\/10.1111\/prd.12262","DOI":"10.1111\/prd.12262"},{"key":"e_1_3_2_7_1","doi-asserted-by":"crossref","unstructured":"Boomsma D Busjahn A Peltonen L. 2002. Classical twin studies and beyond. Nat Rev Genet. 3(11):872\u2013882. https:\/\/doi.org\/10.1038\/nrg932","DOI":"10.1038\/nrg932"},{"key":"e_1_3_2_8_1","doi-asserted-by":"crossref","unstructured":"Conejero Del Mazo R Garc\u00eda Forc\u00e9n L Navarro Aguilar ME. 2023. Recurrent aphthous stomatitis. Med Clin (Barc). 161(6):251\u2013259. https:\/\/doi.org\/10.1016\/j.medcli.2023.05.007","DOI":"10.1016\/j.medcle.2023.05.014"},{"key":"e_1_3_2_9_1","doi-asserted-by":"crossref","unstructured":"Conley D Rauscher E Dawes C Magnusson PK Siegal ML. 2013. Heritability and the equal environments assumption: evidence from multiple samples of misclassified twins. Behav Genet. 43(5):415\u2013426. https:\/\/doi.org\/10.1007\/s10519-013-9602-1","DOI":"10.1007\/s10519-013-9602-1"},{"key":"e_1_3_2_10_1","doi-asserted-by":"crossref","unstructured":"Cui RZ Bruce AJ Rogers RSIII. 2016. Recurrent aphthous stomatitis. Clin Dermatol. 34(4):475\u2013481. https:\/\/doi.org\/10.1016\/j.clindermatol.2016.02.020","DOI":"10.1016\/j.clindermatol.2016.02.020"},{"key":"e_1_3_2_11_1","doi-asserted-by":"crossref","unstructured":"Felson J. 2014. What can we learn from twin studies? A comprehensive evaluation of the equal environments assumption. Soc Sci Res. 43:184\u2013199. https:\/\/doi.org\/10.1016\/j.ssresearch.2013.10.004","DOI":"10.1016\/j.ssresearch.2013.10.004"},{"key":"e_1_3_2_12_1","doi-asserted-by":"crossref","unstructured":"Guo G Wang J. 2002. The mixed or multilevel model for behavior genetic analysis. Behav Genet. 32(1):37\u201349. https:\/\/doi.org\/10.1023\/a:1014455812027","DOI":"10.1023\/A:1014455812027"},{"key":"e_1_3_2_13_1","doi-asserted-by":"crossref","unstructured":"Hagenbeek FA et al. 2023. Maximizing the value of twin studies in health and behaviour. Nat Hum Behav. 7(6):849\u2013860 https:\/\/doi.org\/10.1038\/s41562-023-01609-6.","DOI":"10.1038\/s41562-023-01609-6"},{"key":"e_1_3_2_14_1","doi-asserted-by":"crossref","unstructured":"Jarrar ZA et al. 2018. Definitive zygosity scores in the peas in the pod questionnaire is a sensitive and accurate assessment of the zygosity of adult twins. Twin Res Hum Genet. 21(2):146\u2013154. https:\/\/doi.org\/10.1017\/thg.2018.9","DOI":"10.1017\/thg.2018.9"},{"key":"e_1_3_2_15_1","doi-asserted-by":"crossref","unstructured":"Joy-Thomas A Lalwani Z Guajardo L Valenza J Fakhouri WD. 2025. The role of genetics in human oral health: a systematic-narrative review. Dent J (Basel). 13(3):133. https:\/\/doi.org\/10.3390\/dj13030133","DOI":"10.3390\/dj13030133"},{"key":"e_1_3_2_16_1","doi-asserted-by":"crossref","unstructured":"Lake RI Thomas SJ Martin NG. 1997. Genetic factors in the aetiology of mouth ulcers. Genet Epidemiol. 14(1):17\u201333. https:\/\/doi.org\/10.1002\/(sici)1098-2272(1997)14:1%3C17::aid-gepi2%3E3.0.co;2-2","DOI":"10.1002\/(SICI)1098-2272(1997)14:1<17::AID-GEPI2>3.0.CO;2-2"},{"key":"e_1_3_2_17_1","unstructured":"Lang V. 2019. ACELONG: Stata module to fit multilevel mixed-effects ACE AE and ADE variance decomposition modes. Boston College Department of Economics; [accessed 2025 Oct 22]. https:\/\/EconPapers.repec.org\/RePEc:boc:bocode:s458402"},{"key":"e_1_3_2_18_1","doi-asserted-by":"crossref","unstructured":"Macgregor S Cornes BK Martin NG Visscher PM. 2006. Bias precision and heritability of self-reported and clinically measured height in Australian twins. Hum Genet. 120(4):571\u2013580. https:\/\/doi.org\/10.1007\/s00439-006-0240-z","DOI":"10.1007\/s00439-006-0240-z"},{"key":"e_1_3_2_19_1","doi-asserted-by":"crossref","unstructured":"Mayhew AJ Meyre D. 2017. Assessing the heritability of complex traits in humans: methodological challenges and opportunities. Curr Genomics. 18(4):332\u2013340. https:\/\/doi.org\/10.2174\/1389202918666170307161450","DOI":"10.2174\/1389202918666170307161450"},{"key":"e_1_3_2_20_1","doi-asserted-by":"crossref","unstructured":"McAdams TA Gregory AM Eley TC. 2013. Genes of experience: explaining the heritability of putative environmental variables through their association with behavioural and emotional traits. Behav Genet. 43(4):314\u2013328. https:\/\/doi.org\/10.1007\/s10519-013-9591-0","DOI":"10.1007\/s10519-013-9591-0"},{"key":"e_1_3_2_21_1","doi-asserted-by":"crossref","unstructured":"Miller MF Garfunkel AA Ram C Ship II. 1977. Inheritance patterns in recurrent aphthous ulcers: twin and pedigree data. Oral Surg Oral Med Oral Pathol. 43(6):886\u2013891. https:\/\/doi.org\/10.1016\/0030-4220(77)90081-0","DOI":"10.1016\/0030-4220(77)90081-0"},{"key":"e_1_3_2_22_1","doi-asserted-by":"crossref","unstructured":"Moayyeri A Hammond CJ Hart DJ Spector TD. 2013. The UK adult twin registry (TwinsUK resource). Twin Res Hum Genet. 16(1):144\u2013149. https:\/\/doi.org\/10.1017\/thg.2012.89","DOI":"10.1017\/thg.2012.89"},{"key":"e_1_3_2_23_1","doi-asserted-by":"crossref","unstructured":"Neale MC Cardon LR. 1992. Methodology for genetic studies of twins and families. Kluwer Academic Publishers.","DOI":"10.1007\/978-94-015-8018-2"},{"key":"e_1_3_2_24_1","doi-asserted-by":"crossref","unstructured":"Plomin R Bergeman CS. 1991. The nature of nurture: genetic influence on \u201cenvironmental\u201d measures. Behav Brain Sci. 14(3):373\u2013386. https:\/\/doi.org\/10.1017\/S0140525X00070278","DOI":"10.1017\/S0140525X00070278"},{"key":"e_1_3_2_25_1","doi-asserted-by":"crossref","unstructured":"Rabe-Hesketh S Skrondal A Gjessing HK. 2008. Biometrical modeling of twin and family data using standard mixed model software. Biometrics. 64(1):280\u2013288. https:\/\/doi.org\/10.1111\/j.1541-0420.2007.00803.x","DOI":"10.1111\/j.1541-0420.2007.00803.x"},{"key":"e_1_3_2_26_1","doi-asserted-by":"crossref","unstructured":"Riveros-Gomez I et al. 2024. Aphthous stomatitis\u2014computational biology suggests external biotic stimulus and immunogenic cell death involved. BMC Oral Health. 24(1):1154. https:\/\/doi.org\/10.1186\/s12903-024-04917-z","DOI":"10.1186\/s12903-024-04917-z"},{"key":"e_1_3_2_27_1","doi-asserted-by":"crossref","unstructured":"Robette N G\u00e9nin E Clerget-Darpoux F. 2022. Heritability: what\u2019s the point? What is it not for? A human genetics perspective. Genetica. 150(3\u20134):199\u2013208. https:\/\/doi.org\/10.1007\/s10709-022-00149-7","DOI":"10.1007\/s10709-022-00149-7"},{"key":"e_1_3_2_28_1","doi-asserted-by":"crossref","unstructured":"Rogers RS3rd. 1997. Recurrent aphthous stomatitis: clinical characteristics and associated systemic disorders. Semin Cutan Med Surg. 16(4):278\u2013283. https:\/\/doi.org\/10.1016\/s1085-5629(97)80017-x","DOI":"10.1016\/S1085-5629(97)80017-X"},{"key":"e_1_3_2_29_1","doi-asserted-by":"crossref","unstructured":"Scully C Porter S. 2008. Oral mucosal disease: recurrent aphthous stomatitis. Br J Oral Maxillofac Surg. 46(3):198\u2013206. https:\/\/doi.org\/10.1016\/j.bjoms.2007.07.201","DOI":"10.1016\/j.bjoms.2007.07.201"},{"key":"e_1_3_2_30_1","doi-asserted-by":"crossref","unstructured":"Sharma S Gibbons A Saphire EO. 2025. Sex differences in tissue-specific immunity and immunology. Science. 389(6760):599\u2013603. https:\/\/doi.org\/10.1126\/science.adx4381","DOI":"10.1126\/science.adx4381"},{"key":"e_1_3_2_31_1","doi-asserted-by":"crossref","unstructured":"Slebioda Z Szponar E Kowalska A. 2013. Recurrent aphthous stomatitis: genetic aspects of etiology. Postepy Dermatol Alergol. 30(2):96\u2013102. https:\/\/doi.org\/10.5114\/pdia.2013.34158","DOI":"10.5114\/pdia.2013.34158"},{"key":"e_1_3_2_32_1","doi-asserted-by":"crossref","unstructured":"Slebioda Z Szponar E Kowalska A. 2014. Etiopathogenesis of recurrent aphthous stomatitis and the role of immunologic aspects: literature review. Arch Immunol Ther Exp (Warsz). 62(3):205\u2013215. https:\/\/doi.org\/10.1007\/s00005-013-0261-y","DOI":"10.1007\/s00005-013-0261-y"},{"key":"e_1_3_2_33_1","doi-asserted-by":"crossref","unstructured":"Stoopler ET Villa A Bindakhil M D\u00edaz DLO Sollecito TP. 2024. Common oral conditions: a review. JAMA. 331(12):1045\u20131054. https:\/\/doi.org\/10.1001\/jama.2024.0953","DOI":"10.1001\/jama.2024.0953"},{"key":"e_1_3_2_34_1","doi-asserted-by":"crossref","unstructured":"Tamimy Z et al. 2021. Multilevel twin models: geographical region as a third level variable. Behav Genet. 51(3):319\u2013330. https:\/\/doi.org\/10.1007\/s10519-021-10047-x","DOI":"10.1007\/s10519-021-10047-x"},{"key":"e_1_3_2_35_1","doi-asserted-by":"crossref","unstructured":"Tappuni AR Kovacevic T Shirlaw PJ Challacombe SJ. 2013. Clinical assessment of disease severity in recurrent aphthous stomatitis. J Oral Pathol Med. 42(8):635\u2013641. https:\/\/doi.org\/10.1111\/jop.12059","DOI":"10.1111\/jop.12059"},{"key":"e_1_3_2_36_1","doi-asserted-by":"crossref","unstructured":"Verdi S et al. 2019. TwinsUK: the UK adult twin registry update. Twin Res Hum Genet. 22(6):523\u2013529. https:\/\/doi.org\/10.1017\/thg.2019.65","DOI":"10.1017\/thg.2019.65"},{"key":"e_1_3_2_37_1","doi-asserted-by":"crossref","unstructured":"Verweij KJH Mosing MA Zietsch BP Medland SE. 2012. Estimating heritability from twin studies. In: Elston RC Satagopan JM Sun S editors. Statistical human genetics: methods and protocols. Humana Press. p 151\u2013170. https:\/\/doi.org\/10.1007\/978-1-61779-555-8_9","DOI":"10.1007\/978-1-61779-555-8_9"},{"key":"e_1_3_2_38_1","doi-asserted-by":"crossref","unstructured":"Visscher PM. 2004. Power of the classical twin design revisited. Twin Res. 7(5):505\u2013512. https:\/\/doi.org\/10.1375\/1369052042335250","DOI":"10.1375\/1369052042335250"},{"key":"e_1_3_2_39_1","doi-asserted-by":"crossref","unstructured":"von Elm E et al. 2007. The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. PLoS Med. 4(10):e296. https:\/\/doi.org\/10.1371\/journal.pmed.0040296","DOI":"10.1371\/journal.pmed.0040296"},{"key":"e_1_3_2_40_1","doi-asserted-by":"crossref","unstructured":"Wang Z et al. 2022. Recent advances in the aetiology of recurrent aphthous stomatitis (RAS). Postgrad Med J. 98(1155):57\u201366. https:\/\/doi.org\/10.1136\/postgradmedj-2020-139421","DOI":"10.1136\/postgradmedj-2020-139421"},{"key":"e_1_3_2_41_1","doi-asserted-by":"crossref","unstructured":"Wu D Xin J Liu J Zhou P. 2018. The association between interleukin polymorphism and recurrent aphthous stomatitis: a meta-analysis. Arch Oral Biol. 93:3\u201311. https:\/\/doi.org\/10.1016\/j.archoralbio.2018.05.011","DOI":"10.1016\/j.archoralbio.2018.05.011"},{"key":"e_1_3_2_42_1","doi-asserted-by":"crossref","unstructured":"Yousefi H et al. 2022. Role of genetic polymorphisms in recurrent aphthous stomatitis: a systematic review and meta-analysis. Cytokine. 153:155864. https:\/\/doi.org\/10.1016\/j.cyto.2022.155864","DOI":"10.1016\/j.cyto.2022.155864"}],"container-title":["Journal of Dental Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/00220345261431154","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/00220345261431154","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/00220345261431154","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T20:55:01Z","timestamp":1793566501000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/00220345261431154"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,28]]},"references-count":41,"alternative-id":["10.1177\/00220345261431154"],"URL":"https:\/\/doi.org\/10.1177\/00220345261431154","relation":{},"ISSN":["0022-0345","1544-0591"],"issn-type":[{"value":"0022-0345","type":"print"},{"value":"1544-0591","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,28]]},"article-number":"00220345261431154"}}