Genetic regulation of disease risk and endometrial gene expression highlights potential target genes for endometriosis and polycystic ovarian syndrome.

Fung, Jenny N; Mortlock, Sally; Girling, Jane E; Holdsworth-Carson, Sarah J; Teh, Wan Tinn; Zhu, Zhihong; Lukowski, Samuel W; Mc Kinnon, Brett; McRae, Allan; Yang, Jian; Healey, Martin; Powell, Joseph E; Rogers, Peter A W; Montgomery, Grant W (2018). Genetic regulation of disease risk and endometrial gene expression highlights potential target genes for endometriosis and polycystic ovarian syndrome. Scientific Reports, 8(1), p. 11424. Nature Publishing Group 10.1038/s41598-018-29462-y

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Gynaecology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Endometriose und gynäkologische Onkologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Endometriose und gynäkologische Onkologie

UniBE Contributor:

Mc Kinnon, Brett

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2045-2322

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Monika Zehr

Date Deposited:

01 Apr 2019 15:25

Last Modified:

23 Oct 2019 07:24

Publisher DOI:

10.1038/s41598-018-29462-y

PubMed ID:

30061686

BORIS DOI:

10.7892/boris.125876

URI:

https://boris.unibe.ch/id/eprint/125876

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