Molecular Genetics of Endometriosis


Endometriosis is a gynaecological disease that affects 6–10% of women of reproductive age. Symptoms vary but commonly include severe menstrual and pelvic pain and infertility, all of which can have major impacts on the lives of affected women. Linkage studies have identified several chromosomal regions but the genes contributing to these linkage signals have yet to be identified. Candidate gene studies on over 80 genes have not shown robust evidence of association, mostly due to the limited power to detect individual risk variants of small effects. Four groups have now conducted genome‐wide association studies for endometriosis, revealing a number of intriguing candidates that may contribute to disease risk. Further research aimed at increasing our understanding of the genes and biological pathways underlying endometriosis may provide better and more targeted diagnosis and treatment options in the future.

Key Concepts:

  • Endometriosis is a gynaecological disease that occurs when tissue resembling endometrium (the tissue that lines the inside of the uterus) attaches and grows on organs in the body cavity, including the ovaries, fallopian tubes, intestine and bowel.

  • Endometriosis affects 6–10% of women during their reproductive years and the symptoms, including severe menstrual and pelvic pain and sub‐ or infertility, can greatly impact an affected woman's physical and psychological wellbeing as well as her family and working life.

  • The financial cost of endometriosis is amongst the highest of all complex diseases, with direct (medical and surgical treatment) and indirect (loss of income, reduced productivity, infertility treatment and social withdrawal) health care costs estimated at >$15 billion annually in the US alone.

  • Linkage studies on large numbers of families have indicated chromosomal regions that may harbour endometriosis susceptibility genes but these are yet to be definitively identified.

  • Candidate gene association studies on over 80 genes have not produced convincing evidence of gene robustly associated with endometriosis susceptibility.

  • Genome‐wide association studies have identified a small number of chromosomal areas that harbour extremely interesting candidate genes that should be followed up in the future.

  • Understanding the genes and biological pathways underlying susceptibility to endometriosis may eventually lead to better diagnostic and treatment options for women affected by this common and often debilitating disease.

Keywords: genetics; gene mapping; candidate genes; linkage; genome‐wide association; endometriosis

Figure 1.

Genome‐wide association results for the discovery sample including 3194 endometriosis cases and 7060 controls of European ancestry (Painter et al., ). The P‐value for our best ‘hit’ on chromosome 7 reached genome‐wide significance (P<5.8×10−8) when the replication sample was included in the analysis.

Figure 2.

SNAP plot of genome‐wide association results for chromosome 1 around the WNT4 gene (Painter et al., ). Our results replicated signal from a Japanese endometriosis GWAS (Uno et al., ): the red colour indicates the level of linkage disequilibrium in Caucasians between GWA SNPs in the region and the replicated SNP rs7521902. (SNAP plot created using



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Further Reading

Lee SH, Wray NR, Goddard ME and Visscher PM (2011) Estimating missing heritability for disease from genome‐wide association studies. American Journal of Human Genetics 88: 294–305.

Yang J, Lee SH, Goddard ME and Visscher PM (2011) GCTA: a tool for genome‐wide complex trait analysis. American Journal of Human Genetics 88: 76–82.

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How to Cite close
Painter, Jodie N, Zondervan, Krina T, Missmer, Stacey A, and Montgomery, Grant W(Sep 2011) Molecular Genetics of Endometriosis. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0021473]