Genetics of endometriosis: State of the art on genetic risk factors for endometriosis

Developments in high-throughput genotyping technology have driven discovery of genomic regions associated with an increased risk of endometriosis. In all, 16 genomic regions have been associated with risk of endometriosis in one or more populations. The latest meta-analysis including 17,045 endometriosis cases identified 14 genomic regions supported by results from multiple studies. No independent associations were identified from direct genotyping of common and low-frequency protein-coding variants. This suggests that the most common genetic factors that contribute to endometriosis risk are located in regulatory DNA sequences and alter the regulation of gene transcription. Evidence from different methods is essential to identify the target genes and transcripts that contribute to altered disease risk. Potential target genes in three chromosome regions showing altered gene regulation include LINC00339 and CDC42 on chromosome 1, CDKN2A-AS1 on chromosome 9, and VEZT on chromosome 12. Further functional studies are needed to confirm the causal genes in these and other regions to understand pathways that increase endometriosis risk and help identify novel targets for interventions to improve diagnosis and treatment.