Генетические основы коморбидности эндометриоза

Введение. Результаты ряда исследований свидетельствуют о коморбидности эндометриоза с различными заболеваниями, такими как миома матки, рак эндометрия, мигрень, депрессия, бесплодие, бронхиальная астма, а также заболевания желудка.

Цель. Представить данные литературы о коморбидности эндометриоза и различных заболеваний.

Материалы и методы. Проведен обзор литературы за 2010–2023 гг. в базах PubMed (National Library of Medicine), Cochrane Library, CyberLeninka, Medline, а также в базах данных научного цитирования (Scopus, Web of Science).

Результаты и обсуждение. Установлено, что в основе коморбидности эндометриоза и описанных болезней лежат общность факторов риска (ранний возраст наступления менархе, поздняя менопауза, отсутствие родов в анамнезе, хронические воспалительные заболевания органов малого таза, курение, хронический стресс, воздействие фталатных эфиров), молекулярно-патогенетических механизмов (изменения экспрессии генов, уровня половых гормонов, аберрантный иммунный ответ, субклиническая воспалительная реакция, гиперэстрогения, характерные как для эндометриоза, так и для коморбидных болезней), а также генов, которые участвуют в развитии данных заболеваний. По результатам проведенных полногеномных исследований установлено более 170 полиморфных локусов, ассоциированных с развитием эндометриоза и различных коморбидных заболеваний, выявлена положительная корреляция между эндометриозом и данными болезнями.

Заключение. Проведенные исследования диктуют необходимость учитывать в клинической практике синтропию эндометриоза с другими заболеваниями, что, в свою очередь, требует мультидисциплинарного подхода к ведению пациенток с эндометриозом.

1. Адамян ЛВ, Андреева ЕН. Эндометриоз и его глобальное влияние на организм женщины. Проблемы репродукции. 2022;28(1):54–64. https://doi.org/10.17116/repro20222801154.

2. Eisenberg VH, Weil C, Chodick G, Shalev V. Epidemiology of endometriosis: a large population-based database study from a healthcare provider with 2 million members. BJOG. 2018;125(1):55–62. https://doi.org/10.1111/1471-0528.14711.

3. Волкова СВ, Абитова МЗ, Михалева ЛМ, Хамошина МБ, Оразов МР. Причины бесплодия при эндометриозе: версии и контраверсии XXI в. Акушерство и гинекология: новости, мнения, обучение. 2020;8(3):110–114. Режим доступа: https://elibrary.ru/uhykut.

4. Laganà AS, Garzon S, Götte M, Viganò P, Franchi M, Ghezzi F, Martin DC. The Pathogenesis of Endometriosis: Molecular and Cell Biology Insights. Int J Mol Sci. 2019;20(22):5615. https://doi.org/10.3390/ijms20225615.

5. Сухих ГТ, Серов ВН, Адамян ЛВ, Баранов ИИ, Беженарь ВФ, Габидуллина РИ и др. Алгоритмы ведения пациенток с эндометриозом: согласованная позиция экспертов Российского общества акушеров-гинекологов. Акушерство и гинекология. 2023;(5):159–176. https://doi.org/10.18565/aig.2023.132.

6. Самойлова АВ, Гунин АГ, Сидоров АЕ, Денисова ТГ, Чернышов ВВ, Смирнова ТЛ. Современные направления изучения этиологии и патогенеза эндометриоза (обзор литературы). Проблемы репродукции. 2020;26(5):118–132. https://doi.org/10.17116/repro202026051118.

7. McGrath IM, Montgomery GW, Mortlock S. Insights from Mendelian randomization and genetic correlation analyses into the relationship between endometriosis and its comorbidities. Hum Reprod Update. 2023;29(5):655–674. https://doi.org/10.1093/humupd/dmad009.

8. Feinstein AR. The pre-therapeutic classification of co-morbidity in chronic disease. J Chronic Dis. 1970;23(7):455–468. https://doi.org/10.1016/0021-9681(70)90054-8.

9. Makovski TT, Schmitz S, Zeegers MP, Stranges S, van den Akker M. Multimorbidity and quality of life: Systematic literature review and meta-analysis. Ageing Res Rev. 2019;53:100903. https://doi.org/10.1016/j.arr.2019.04.005.

10. Kuan V, Denaxas S, Patalay P, Nitsch D, Mathur R, GonzalezIzquierdo A. Identifying and visualising multimorbidity and comorbidity patterns in patients in the English National Health Service: a populationbased study. Lancet Digit Health. 2023;5(1):e16–e27. https://doi.org/10.1016/S2589-7500(22)00187-X.

11. Пузырев ВП. Генетические основы коморбидности у человека. Генетика. 2015;51(4):491–502. https://doi.org/10.7868/S0016675815040098.

12. Туманова УН, Щеголев АИ, Павлович СВ, Серов ВН. Факторы риска развития эндометриоза. Акушерство и гинекология. 2020;(2):68–75. https://doi.org/10.18565/aig.2020.2.68-75.

13. Пономаренко ИВ, Полоников АВ, Верзилина ИН, Чурносов МИ. Молекулярно-генетические детерминанты развития эндометриоза. Вопросы гинекологии, акушерства и перинатологии. 2019;18(1):82–86. https://doi.org/10.20953/1726-1678-2019-1-82-86.

14. Пузырев ВП, Фрейдин МБ. Генетический взгляд на феномен сочетанных заболеваний человека. Acta Naturae. 2009;1(3):57–63. Режим доступа: https://elibrary.ru/mudadl.

15. Головченко ИО. Генетические детерминанты уровня половых гормонов у больных эндометриозом. Научные результаты биомедицинских исследований. 2023;9(1):5–21. https://doi.org/10.18413/2658-6533-2023-9-1-0-1.

16. Радзинский ВЕ, Алтухова ОБ. Молекулярно-генетические детерминанты бесплодия при генитальном эндометриозе. Научные результаты биомедицинских исследований. 2018;4(3):28–37. https://doi.org/10.18413/2313-8955-2018-4-3-0-3.

17. Ponomarenko MS, Reshetnikov EA, Churnosova MM, Reshetnikova YuN, Churnosov VI, Ponomarenko IV. Comorbidity and syntropy of benign proliferative diseases of the female reproductive system: non-genetic, genetic, and epigenetic factors (review). Research Results in Biomedicine. 2023;9(4):544–556. https://doi.org/10.18413/2658-6533-2023-9-4-0-9.

18. Пономарева ТА, Алтухова ОБ, Пономаренко ИВ, Чурносов МИ. Роль генетических факторов в формировании эндометриоидных поражений. Акушерство, гинекология и репродукция. 2023;17(4):443–454. https://doi.org/10.17749/2313-7347/ob.gyn.rep.2023.434.

19. Демакова НА. Молекулярно-генетические характеристики пациенток с гиперплазией и полипами эндометрия. Научный результат. Медицина и фармация. 2018;4(2):26–39. https://doi.org/10.18413/2313-8955-2018-4-2-0-4.

20. Nezhat C, Li A, Abed S, Balassiano E, Soliemannjad R, Nezhat A et al. Strong Association Between Endometriosis and Symptomatic Leiomyomas. JSLS. 2016;20(3):e2016.00053. https://doi.org/10.4293/JSLS.2016.00053.

21. Lin KY, Yang CY, Lam A, Chang CY, Lin WC. Uterine leiomyoma is associated with the risk of developing endometriosis: A nationwide cohort study involving 156,195 women. PLoS ONE. 2021;16(8):e0256772. https://doi.org/10.1371/journal.pone.0256772.

22. Пономаренко ИВ, Полоников АВ, Чурносов МИ. Молекулярные механизмы и факторы риска развития эндометриоза. Акушерство и гинекология. 2019;(3):26–31. https://doi.org/10.18565/aig.2019.3.26-31.

23. Uimari O, Nazri H, Tapmeier T. Endometriosis and Uterine Fibroids (Leiomyomata): Comorbidity, Risks and Implications. Front Reprod Health. 2021;3:750018. https://doi.org/10.3389/frph.2021.750018.

24. Баранов ВС. Эндометриоз и миома матки с позиции системной генетики. Журнал акушерства и женских болезней. 2016;65(S):5–7. Режим доступа: https://cyberleninka.ru/article/n/endometrioz-i-mioma-matki-spozitsii-sistemnoy-genetiki.

25. Gallagher CS, Mäkinen, Harris HR, Rahmioglu N, Uimari O, Cook JP et al. Genome-wide association and epidemiological analyses reveal common genetic origins between uterine leiomyomata and endometriosis. Nat Commun. 2019;10(1):4857. https://doi.org/10.1038/s41467-019-12536-4.

26. Masuda T, Low SK, Akiyama M, Hirata M, Ueda Y, Matsuda K et al. GWAS of five gynecologic diseases and cross-trait analysis in Japanese. Eur J Hum Genet. 2020;28(1):95–107. https://doi.org/10.1038/s41431-019-0495-1.

27. Govindan S, Shaik NA, Vedicherla B, Kodati V, Rao KP, Hasan Q. Estrogen receptor-alpha gene (T/C) Pvu II polymorphism in endometriosis and uterine fibroids. Dis Markers. 2009;26(4):149–154. https://doi.org/10.3233/ DMA-2009-0625.

28. Hsieh YY, Chang CC, Tsai FJ, Lin CC, Tsai CH. T homozygote and allele of epidermal growth factor receptor 2073 gene polymorphism are associated with higher susceptibility to endometriosis and leiomyomas. Fertil Steril. 2005;83(3):796–799. https://doi.org/10.1016/j.fertnstert.2004.08.032.

29. Hsieh YY, Lee CC, Chang CC, Wang YK, Yeh LS, Lin CS. Angiotensin I-converting enzyme insertion-related genotypes and allele are associated with higher susceptibility of endometriosis and leiomyoma. Mol Reprod Dev. 2007;74(7):808–814. https://doi.org/10.1002/mrd.20474.

30. Bonavina G, Taylor HS. Endometriosis-associated infertility: From pathophysiology to tailored treatment. Front Endocrinol. 2022;13:1020827. https://doi.org/10.3389/fendo.2022.1020827.

31. Abu Hashim H, Elaraby S, Fouda AA, Rakhawy ME. The prevalence of adenomyosis in an infertile population: a cross-sectional study. Reprod Biomed Online. 2020;40(6):842–850. https://doi.org/10.1016/j.rbmo.2020.02.011.

32. Filip L, Duică F, Prădatu A, Crețoiu D, Suciu N, Crețoiu SM et al. Endometriosis Associated Infertility: A Critical Review and Analysis on Etiopathogenesis and Therapeutic Approaches. Medicina. 2020;56(9):460. https://doi.org/10.3390/medicina56090460.

33. Broi MGD, Ferriani RA, Navarro PA. Ethiopathogenic mechanisms of endometriosis-related infertility. JBRA Assist Reprod. 2019;23(3):273–280. https://doi.org/10.5935/1518-0557.20190029.

34. Rahmioglu N, Mortlock S, Ghiasi M, Møller PL, Stefansdottir L, Galarneau G et al. The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions. Nat Genet. 2023;55(3):423–436. https://doi.org/10.1038/s41588-023-01323-z.

35. Kanellopoulos D, Karagianni D, Pergialiotis V, Nikitheas N, Lazaris AK, Iliopoulos D. Endometriosis and Infertility: A Review of the Literature. Maedica. 2022;17(2):458–463. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC9375884/.

36. Zulli K, Bianco B, Mafra FA, Teles JS, Christofolini DM, Barbosa CP. Polymorphism of the estrogen receptor β gene is related to infertility and infertility-associated endometriosis. Arq Bras Endocrinol Metabol. 2010;54(6):567–571. https://doi.org/10.1590/s0004-27302010000600010.

37. Teles JS, Bianco B, Vilarino FL, André GM, Christofolini DM, Barbosa CP. Association of FCRL3 C-169T promoter single-nucleotide polymorphism with idiopathic infertility and infertility-related endometriosis. J Reprod Immunol. 2011;89(2):212–215. https://doi.org/10.1016/j.jri.2011.02.007.

38. Ruiz LA, Dutil J, Ruiz A, Fourquet J, Abac S, Laboy J, Flores I. Singlenucleotide polymorphisms in the lysyl oxidase-like protein 4 and complement component 3 genes are associated with increased risk for endometriosis and endometriosis-associated infertility. Fertil Steril. 2011;96(2):512–515. https://doi.org/10.1016/j.fertnstert.2011.06.001.

39. Lamp M, Peters M, Reinmaa E, Haller-Kikkatalo K, Kaart T, Kadastik U et al. Polymorphisms in ESR1, ESR2 and HSD17B1 genes are associated with fertility status in endometriosis. Gynecol Endocrinol. 2011;27(6):425–433. https://doi.org/10.3109/09513590.2010.495434.

40. Bianco B, Lerner TG, Trevisan CM, Cavalcanti V, Christofolin DM, Barbosa CP. The nuclear factor-kB functional promoter polymorphism is associated with endometriosis and infertility. Hum Immunol. 2012;73(11):1190–1193. https://doi.org/10.1016/j.humimm.2012.08.008.

41. Paskulin DD, Cunha-Filho JS, Souza CA, Bortolini MC, Hainaut P, AshtonProlla P. TP53 PIN3 and PEX4 polymorphisms and infertility associated with endometriosis or with post-in vitro fertilization implantation failure. Cell Death Dis. 2012;3(9):e392. https://doi.org/10.1038/cddis.2012.116.

42. Wang W, Li Y, Maitituoheti M, Yang R, Wu Z, Wang T et al. Association of an oestrogen receptor gene polymorphism in Chinese Han women with endometriosis and endometriosis-related infertility. Reprod Biomed Online. 2013;26(1):93–98. https://doi.org/10.1016/j.rbmo.2012.09.007.

43. Peluso C, Christofolini DM, Goldman CS, Mafra FA, Cavalcanti V, Barbosa CP, Bianco B. TYK2 rs34536443 polymorphism is associated with a decreased susceptibility to endometriosis-related infertility. Hum Immunol. 2013;74(1):93–97. https://doi.org/10.1016/j.humimm.2012.09.007.

44. Kang S, Li Y, Li B, Wang N, Zhou RM, Zhao XW. Genetic variation of the E-cadherin gene is associated with primary infertility in patients with ovarian endometriosis. Fertil Steril. 2014;102(4):1149–1154. https://doi.org/10.1016/j.fertnstert.2014.07.005.

45. Szczepańska,M, Mostowska A, Wirstlein P, Skrzypczak J, Misztal M, Jagodziński PP. Polymorphic variants in vitamin D signaling pathway genes and the risk of endometriosis-associated infertility. Mol Med Rep. 2015;12(5):7109–7115. https://doi.org/10.3892/mmr.2015.4309.

46. De Conto E, Matte Ú, Bilibio JP, Genro VK, Souza CA, Leão DP, CunhaFilho JS. Endometriosis-associated infertility: GDF-9, AMH, and AMHR2 genes polymorphisms. J Assist Reprod Genet. 2017;34(12):1667–1672. https://doi.org/10.1007/s10815-017-1026-z.

47. Irimia T, Pușcașiu L, Mitranovici MI, Crișan A, Budianu MA, Bănescu C et al. Oxidative-Stress Related Gene Polymorphism in Endometriosis-Associated Infertility. Medicina. 2022;58(8):1105. https://doi.org/10.3390/medicina58081105.

48. Hermens M, van Altena AM, van der Aa M, Bulten J, van Vliet HAAM, Siebers AG, Bekkers RLM. Endometrial cancer prognosis in women with endometriosis and adenomyosis: A retrospective nationwide cohort study of 40 840 women. Int J Cancer. 2022;150(9):1439–1446. https://doi.org/10.1002/ijc.33907.

49. Kalaitzopoulos DR, Mitsopoulou A, Iliopoulou SM, Daniilidis A, Samartzis EP, Economopoulos KP. Association between endometriosis and gynecological cancers: a critical review of the literature. Arch Gynecol Obstet. 2020;301(2):355–367. https://doi.org/10.1007/s00404-020-05445-1.

50. Li J, Liu R, Tang S, Feng F, Liu C, Wang L et al. Impact of endometriosis on risk of ovarian, endometrial and cervical cancers: a meta-analysis. Arch Gynecol Obstet. 2019;299(1):35–46. https://doi.org/10.1007/s00404-018-4968-1.

51. Ye J, Peng H, Huang X, Qi X. The association between endometriosis and risk of endometrial cancer and breast cancer: a meta-analysis. BMC Womens Health. 2022;22(1):455. https://doi.org/10.1186/s12905-022-02028-x.

52. Monnin N, Fattet AJ, Koscinski I. Endometriosis: Update of Pathophysiology, (Epi) Genetic and Environmental Involvement. Biomedicines. 2023;11(3):978. https://doi.org/10.3390/biomedicines11030978.

53. Painter JN, O’Mara TA, Morris AP, Cheng THT, Gorman M, Martin L et al. Genetic overlap between endometriosis and endometrial cancer: evidence from cross-disease genetic correlation and GWAS meta-analyses. Cancer Med. 2018;7(5):1978–1987. https://doi.org/10.1002/cam4.1445.

54. Kho PF, Mortlock S, Endometrial Cancer Association Consortium, International Endometriosis Genetics Consortium, Rogers PAW, Nyholt DR et al. Genetic analyses of gynecological disease identify genetic relationships between uterine fibroids and endometrial cancer, and a novel endometrial cancer genetic risk region at the WNT4 1p36.12 locus. Hum Genet. 2021;140(9):1353–1365. https://doi.org/10.1007/s00439-021-02312-0.

55. Huang Y, Zong L, Lin J, Fu Y, Liu Z, Mao T et al. Association of P53 gene polymorphisms with susceptibility to endometriosis. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2013;30(3):335–339. (In Chinese) https://doi.org/10.3760/cma.j.issn.1003-9406.2013.03.019.

56. Sinaii N, Cleary SD, Ballweg ML, Nieman LK, Stratton P. High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis. Hum Reprod. 2002;17(10):2715–2724. https://doi.org/10.1093/humrep/17.10.2715.

57. Matorras R, Ocerin I, Unamuno M, Nieto A, Peiró E, Burgos J, Expósito A. Prevalence of endometriosis in women with systemic lupus erythematosus and Sjogren’s syndrome. Lupus. 2007;16(9):736–740. https://doi.org/10.1177/0961203307081339.

58. Peng YH, Su SY, Liao WC, Huang CW, Hsu CY, Chen HJ et al. Asthma is associated with endometriosis: A retrospective population-based cohort study. Respir Med. 2017;132:112–116. https://doi.org/10.1016/j.rmed.2017.10.004.

59. Nowakowska A, Kwas K, Fornalczyk A, Wilczyński J, Szubert M. Correlation between Endometriosis and Selected Allergic and Autoimmune Diseases and Eating Habits. Medicina. 2022;58(8):1038. https://doi.org/10.3390/medicina58081038.

60. Giacomini E, Minetto S, Li Piani L, Pagliardini L, Somigliana E, Viganò P. Genetics and Inflammation in Endometriosis: Improving Knowledge for Development of New Pharmacological Strategies. Int J Mol Sci. 2021;22(16):9033. https://doi.org/10.3390/ijms22169033.

61. Adewuyi EO, Mehta D, International Endogene Consortium (IEC), 23andMe Research Team, Nyholt DR. Genetic overlap analysis of endometriosis and asthma identifies shared loci implicating sex hormones and thyroid signalling pathways. Hum Reprod. 2022;37(2):366–383. https://doi.org/10.1093/humrep/deab254.

62. Wu Y, Wang H, Chen S, Lin Y, Xie X, Zhong G, Zhang Q. Migraine Is More Prevalent in Advanced-Stage Endometriosis, Especially When Co-Occuring with Adenomoysis. Front Endocrinol. 2021;12:814474. https://doi.org/10.3389/fendo.2021.814474.

63. Maitrot-Mantelet L, Hugon-Rodin J, Vatel M, Marcellin L, Santulli P, Chapron C, Plu-Bureau G. Migraine in relation with endometriosis phenotypes: Results from a French case-control study. Cephalalgia. 2020;40(6):606–613. https://doi.org/10.1177/0333102419893965.

64. Miller JA, Missmer SA, Vitonis AF, Sarda V, Laufer MR, DiVasta AD. Prevalence of migraines in adolescents with endometriosis. Fertil Steril. 2018;109(4):685–690. https://doi.org/10.1016/j.fertnstert.2017.12.016.

65. Jenabi E, Khazaei S. Endometriosis and migraine headache risk: a meta-analysis. Women Health. 2020;60(8):939–945. https://doi.org/10.1080/03630242.2020.1779905.

66. Pasquini B, Seravalli V, Vannuccini S, La Torre F, Geppetti P, Iannone L et al. Endometriosis and the diagnosis of different forms of migraine: an association with dysmenorrhoea. Reprod Biomed Online. 2023;47(1):71–76. https://doi.org/10.1016/j.rbmo.2023.03.020.

67. Андреев АЕ, Клейменова ТС, Дробинцева АО, Полякова ВО, Кветной ИМ. Сигнальные молекулы, вовлеченные в образование новых нервных окончаний при эндометриозе (обзор). Научные результаты биомедицинских исследований. 2019;5(1):94–107. https://doi.org/10.18413/2313-8955-2019-5-1-0-7.

68. Frankel LR, Medina R, Ashley M, Lopez JL, Concepion L. Status Migrainosus and Endometriosis: A Case Report and Review of the Literature. Cureus. 2021;13(11):e19621. https://doi.org/10.7759/cureus.19621.

69. Voedisch AJ, Hindiyeh N. Combined hormonal contraception and migraine: are we being too strict? Curr Opin Obstet Gynecol. 2019;31(6):452–458. https://doi.org/10.1097/GCO.0000000000000586.

70. Adewuyi EO, Sapkota, Y., International Endogene Consortium Iec, andMe Research Team, International Headache Genetics Consortium Ihgc, Auta A et al. Shared Molecular Genetic Mechanisms Underlie Endometriosis and Migraine Comorbidity. Genes. 2020;11(3):268. https://doi.org/10.3390/genes11030268.

71. Nyholt DR, Gillespie NG, Merikangas KR, Treloar SA, Martin NG, Montgomery GW. Common genetic influences underlie comorbidity of migraine and endometriosis. Genet Epidemiol. 2009;33(2):105–113. https://doi.org/10.1002/gepi.20361.

72. van Barneveld E, Manders J, van Osch FHM, van Poll M, Visser L, van Hanegem N et al. Depression, Anxiety, and Correlating Factors in Endometriosis: A Systematic Review and Meta-Analysis. J Womens Health. 2022;31(2):219–230. https://doi.org/10.1089/jwh.2021.0021.

73. Szypłowska M, Tarkowski R, Kułak K. The impact of endometriosis on depressive and anxiety symptoms and quality of life: a systematic review. Front Public Health. 2023;11:1230303. https://doi.org/10.3389/fpubh.2023.1230303.

74. Koller D, Pathak GA, Wendt FR, Tylee DS, Levey DF, Overstreet C et al. Epidemiologic and Genetic Associations of Endometriosis With Depression, Anxiety, and Eating Disorders. JAMA Netw Open. 2023;6(1):e2251214. https://doi.org/10.1001/jamanetworkopen.2022.51214.

75. Nassiri Kigloo H, Itani R, Montreuil T, Feferkorn I, Raina J, Tulandi T et al. Endometriosis, chronic pain, anxiety, and depression: A retrospective study among 12 million women. J Affect Disord. 2023;346:260–265. https://doi.org/10.1016/j.jad.2023.11.034.

76. Warzecha D, Szymusik I, Wielgos M, Pietrzak B. The Impact of Endometriosis on the Quality of Life and the Incidence of Depression – A Cohort Study. Int J Environ Res Public Health. 2020;17(10):3641. https://doi.org/10.3390/ijerph17103641.

77. Chen LC, Hsu JW, Huang KL, Bai YM, Su TP, Li CT et al. Risk of developing major depression and anxiety disorders among women with endometriosis: A longitudinal follow-up study. J Affect Disord. 2016;190:282–285. https://doi.org/10.1016/j.jad.2015.10.030.

78. Albert KM, Newhouse PA. Estrogen, Stress, and Depression: Cognitive and Biological Interactions. Annu Rev Clin Psychol. 2019;15:399–423. https://doi.org/10.1146/annurev-clinpsy-050718-095557.

79. Adewuyi EO, Mehta D, Sapkota Y, International Endogene Consortium, 23andMe Research Team, Auta A et al. Genetic analysis of endometriosis and depression identifies shared loci and implicates causal links with gastric mucosa abnormality. Hum Genet. 2021;140(3):529–552. https://doi.org/10.1007/s00439-020-02223-6.

80. Junkka SS, Ohlsson B. Associations and gastrointestinal symptoms in women with endometriosis in comparison to women with irritable bowel syndrome: a study based on a population cohort. BMC Gastroenterol. 2023;23(1):228. https://doi.org/10.1186/s12876-023-02861-w.

81. McGrath IM, International Endometriosis Genetics Consortium, Montgomery GW, Mortlock S. Genomic characterisation of the overlap of endometriosis with 76 comorbidities identifies pleiotropic and causal mechanisms underlying disease risk. Hum Genet. 2023;142(9):1345–1360. https://doi.org/10.1007/s00439-023-02582-w.

82. Yang F, Wu Y, Hockey R, International Endometriosis Genetics Consortium, Doust J, Mishra GD et al. Evidence of shared genetic factors in the etiology of gastrointestinal disorders and endometriosis and clinical implications for disease management. Cell Rep Med. 2023;4(11):101250. https://doi.org/10.1016/j.xcrm.2023.101250.