Endometriosis is a chronic inflammatory disease characterised by the growth of endometrial epithelial and stromal cells outside the uterine cavity. It is associated with pelvic pain and puts a significant strain on the individual and health care system. Genome wide association studies have identified 27 regions associated with increased susceptibility to endometriosis. The critical SNPs in each region are intergenic, or intronic. The next critical step is identifying the target genes and we are analysing the genetic effects on gene expression. Expression quantitative trait loci (eQTL) are genetic regions that influence the expression of multiple genes. An overlap between endometriosis associated genetic variants and eQTLs could identify genes related to endometriosis. We previously identified eQTL in endometrial tissue using microarray data identifying eQTLs for 453 unique genes using the Bonferroni genome wide significant threshold. Endometrial tissue however consists of both epithelial and stromal cells and eQTL are tissue and cell specific. It is likely distinct eQTLs may exist in both the epithelial and stromal cells.
Pure populations of endometrial stromal cells were isolated from 59 endometrial biopsies and genome wide genotyping performed and additional single nucleotide polymorphisms imputed using the 1000 genomes project. Genome wide gene expression was determined using RNA-seq and genome-wide genetic influence on gene expression was determined.
The result identify 14,307 genes expressed in 90% of samples with 6,424 cis-eQTL passing the Bonferroni test (p,3.3x10-9) for 111 unique genes. Of these 111 genes, cis-eQTL for 29 genes were not previously detected in whole endometrial tissue. The 29 unique genes are not located within the 27 regions associated with endometriosis. However, the genetic regulation of gene expression in individual cell types from the endometrial tissue should be considered to understand gene regulation in the endometrium and their potential role in complex genetic reproductive disorders.