Oral Presentation Annual Meetings of the Endocrine Society of Australia and Society for Reproductive Biology and Australia and New Zealand Bone and Mineral Society 2016

Genetic regulation of gene expression in human endometrium and across the menstrual cycle (#248)

Jenny N Fung 1 2 , Yadav Sapkota 2 , Jane E Girling 3 , Sarah J Holdsworth-Carson 3 , Peter AW Rogers 3 , Joseph E Powell 1 , Grant W Montgomery 1 2
  1. Institute for Molecular Bioscience, Brisbane, QLD, Australia
  2. QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
  3. Department of Obstetrics & Gynaecology, University of Melbourne, Melbourne

Human endometrium is essential for establishment and maintenance of pregnancy and plays a central role in female fertility. It is a dynamic tissue undergoing cyclical breakdown and regeneration across the menstrual cycle. Gene expression also varies between individuals and extensive studies show that expression levels for many genes are under genetic control. These genetic effects are called expression quantitative traits loci (eQTLs) and genetic effects on common diseases can be mediated through effects of eQTLs. To better understand mechanisms underlying the gene regulation in the endometrium and across the menstrual cycle, we mapped eQTLs in endometrial tissue from 123 women with European ancestry. DNA samples from blood were genotyped on Illumina HumanCoreExome chips. Total RNA was extracted from endometrial tissues from the same individuals. Whole-transcriptome profiles were characterized using Illumina Human HT-12 v4.0 Expression Beadchips. We performed eQTL mapping with ~5,000,000 genotyped and imputed SNPs and 15,226 probes for 12,329 unique genes with detectable expression. SNPs showing association with gene expression located within a 250kb window of the associated probe were defined as local (cis-acting) eQTLs. We observed 18,595 cis SNP-probe associations at a study-wide level of significance (p < 1x10-7 threshold). There were a total of 211 probes, mapping to 198 unique genes, with at least one significant eQTL. The strongest eQTLs in endometrium were CHURC1, ZP3 and IPO8 (p < 8.34x10-30). Gene expression levels vary considerably across the menstrual cycle. We further performed a context-specific eQTL analysis to investigate if genetic effects on gene expression regulation act in a menstrual cycle-specific manner. We observed that the magnitude of genotype effects on gene expression was similar across the menstrual cycle stages for most eQTLs. Taken together, these data demonstrated strong genetic effects on gene expression in endometrium with similar effects across the menstrual cycle.