Endometriosis is a complex disease and despite affecting one in nine Australian women, and others who are transgender, gender diverse, undiagnosed or misdiagnosed, the exact cause remains unknown.

However, considerable research suggests that both genetic and environmental factors are involved in causing endometriosisi.

Large population studies support a genetic link, where high rates of endometriosis are reported among relatives, for example daughters or sister/s of individuals with endometriosis.

A highly cited study from Australia, estimated the genetic contribution to risk, or heritability, of endometriosis is approximately 50%ii. However, there is no single gene that causes endometriosis.

A recent genome-wide association study (GWAS) meta-analysis, including 60,674 cases and 701,926 controls, reports 42 genome-wide significant loci (or specific regions in the DNA) associated with endometriosis riskiii. Therefore, genetic risk for endometriosis results from the combined effects of a large number of genetic variants, each with small effects on disease risk, typical of complex diseasesiv.

To further complicate matters, often these loci of interest are found in non-coding regions of the DNA, making their causality even more difficult to determine. A repeated finding however, is that many of the identified variants associated with endometriosis have larger effects in those patients with more severe (e.g. stage 3-4) endometriosisv.

This finding supports the suggestion that endometriosis lesions (superficial, deep and ovarian) represent distinct subtypes. In fact, studies have demonstrated different gene expression profiles between endometrioma and peritoneal lesionsvi. Exploring the genetics of endometriosis continues to be a huge focus of researchers, with the intention to find which combination of genetic variants contributes to increased risk for endometriosis.

Centre of Excellence

Julia Argyrou Endometriosis Centre at Epworth

Keep learning about endometriosis. 

i Stefansson H, Geirsson RT, Steinthorsdottir V, Jonsson H, Manolescu A, Kong A, Ingadottir G, Gulcher J, Stefansson K. Genetic factors contribute to the risk of developing endometriosis. Hum Reprod. 2002 Mar;17(3):555-9. doi: 10.1093/humrep/17.3.555. PMID: 11870102.

ii Treloar SA, O'Connor DT, O'Connor VM, Martin NG. Genetic influences on endometriosis in an Australian twin sample. [email protected]. Fertil Steril. 1999 Apr;71(4):701-10. doi: 10.1016/s0015-0282(98)00540-8. PMID: 10202882.

iii Rahmioglu N, Mortlock S, Ghiasi M, Møller PL, Stefansdottir L, Galarneau G, Turman C, Danning R, Law MH, Sapkota Y, Christofidou P, Skarp S, Giri A, Banasik K, Krassowski M, Lepamets M, Marciniak B, Nõukas M, Perro D, Sliz E, Sobalska-Kwapis M, Thorleifsson G, Topbas-Selcuki NF, Vitonis A, Westergaard D, Arnadottir R, Burgdorf KS, Campbell A, Cheuk CSK, Clementi C, Cook J, De Vivo I, DiVasta A, Dorien O, Donoghue JF, Edwards T, Fontanillas P, Fung JN, Geirsson RT, Girling JE, Harkki P, Harris HR, Healey M, Heikinheimo O, Holdsworth-Carson S, Hostettler IC, Houlden H, Houshdaran S, Irwin JC, Jarvelin MR, Kamatani Y, Kennedy SH, Kepka E, Kettunen J, Kubo M, Kulig B, Kurra V, Laivuori H, Laufer MR, Lindgren CM, MacGregor S, Mangino M, Martin NG, Matalliotaki C, Matalliotakis M, Murray AD, Ndungu A, Nezhat C, Olsen CM, Opoku-Anane J, Padmanabhan S, Paranjpe M, Peters M, Polak G, Porteous DJ, Rabban J, Rexrode KM, Romanowicz H, Saare M, Saavalainen L, Schork AJ, Sen S, Shafrir AL, Siewierska-Górska A, Słomka M, Smith BH, Smolarz B, Szaflik T, Szyłło K, Takahashi A, Terry KL, Tomassetti C, Treloar SA, Vanhie A, Vincent K, Vo KC, Werring DJ, Zeggini E, Zervou MI; DBDS Genomic Consortium; FinnGen Study; FinnGen Endometriosis Taskforce; Celmatix Research Team; 23andMe Research Team; Adachi S, Buring JE, Ridker PM, D'Hooghe T, Goulielmos GN, Hapangama DK, Hayward C, Horne AW, Low SK, Martikainen H, Chasman DI, Rogers PAW, Saunders PT, Sirota M, Spector T, Strapagiel D, Tung JY, Whiteman DC, Giudice LC, Velez-Edwards DR, Uimari O, Kraft P, Salumets A, Nyholt DR, Mägi R, Stefansson K, Becker CM, Yurttas-Beim P, Steinthorsdottir V, Nyegaard M, Missmer SA, Montgomery GW, Morris AP, Zondervan KT. The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions. Nat Genet. 2023 Mar;55(3):423-436. doi: 10.1038/s41588-023-01323-z. Epub 2023 Mar 13. PMID: 36914876; PMCID: PMC10042257.

iv Montgomery GW, Mortlock S, Giudice LC. Should Genetics Now Be Considered the Pre-eminent Etiologic Factor in Endometriosis? J Minim Invasive Gynecol. 2020 Feb;27(2):280-286. doi: 10.1016/j.jmig.2019.10.020. Epub 2019 Nov 1. PMID: 31683028; PMCID: PMC7863762.

v Montgomery GW, Mortlock S, Giudice LC. Should Genetics Now Be Considered the Pre-eminent Etiologic Factor in Endometriosis? J Minim Invasive Gynecol. 2020 Feb;27(2):280-286. doi: 10.1016/j.jmig.2019.10.020. Epub 2019 Nov 1. PMID: 31683028; PMCID: PMC7863762.

vi Marla S, Mortlock S, Heinosalo T, Poutanen M, Montgomery GW, McKinnon BD. Gene expression profiles separate endometriosis lesion subtypes and indicate a sensitivity of endometrioma to estrogen suppressive treatments through elevated ESR2 expression. BMC Med. 2023 Nov 23;21(1):460. doi: 10.1186/s12916-023-03166-1. PMID: 37996888; PMCID: PMC10666321.

19 December 2023


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