Abstract
Gene expression varies markedly across the menstrual cycle and expression levels for many genes are under genetic control. We analyzed gene expression and mapped expression quantitative trait loci (eQTLs) in endometrial tissue samples from 229 women and then analyzed the overlap of endometrial eQTL signals with genomic regions associated with endometriosis and other reproductive traits. We observed a total of 45,923 cis-eQTLs for 417 unique genes and 2,968 trans-eQTLs affecting 82 unique genes. Two eQTLs were located in known risk regions for endometriosis including LINC00339 on chromosome 1 and VEZT on chromosome 12 and there was evidence for eQTLs that may be target genes in genomic regions associated with other reproductive diseases. Dynamic changes in expression of individual genes across cycle include alterations in both mean expression and transcriptional silencing. Significant effects of cycle stage on mean expression levels were observed for (2,427/15,262) probes with detectable expression in at least 90% of samples and for (2,877/9,626) probes expressed in some, but not all samples. Pathway analysis supports similar biological control of both altered expression levels and transcriptional silencing. Taken together, these data identify strong genetic effects on genes with diverse functions in human endometrium and provide a platform for better understanding genetic effects on endometrial-related pathologies.
Highlights
Hardy-Weinberg Equilibrium (HWE) p < 1 × 10−6 (–hwe 0.000001 command) were removed leaving 282,625 SNPs for imputation
We analyzed genetic regulation of gene expression in endometrium in a large sample to increase the power for detection of eQTLs and analyze the overlap of eQTL signals with genomic regions associated with endometriosis and other reproductive traits
Methods for eQTL analysis generally restrict the data to probes/ genes expressed in >90% of samples in a study
Summary
The aims of this study were to expand the sample size to increase the power of our eQTL studies in endometrium and conduct formal analyses of the overlap between endometrial eQTLs and genetic variants associated with risk for endometriosis and other reproductive traits
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