Sapkota, Yadav, De Vivo, Immaculata, Steinthorsdottir, Valgerdur, Fassbender, Amelie, Bowdler, Lisa, Buring, Julie E, Edwards, Todd L, Jones, Sarah, Dorien, O, Peterse, Danielle et al (show 15 more authors)
(2017)
Analysis of potential protein-modifying variants in 9000 endometriosis patients and 150000 controls of European ancestry.
SCIENTIFIC REPORTS, 7 (1).
11380-.
Abstract
Genome-wide association (GWA) studies have identified 19 independent common risk loci for endometriosis. Most of the GWA variants are non-coding and the genes responsible for the association signals have not been identified. Herein, we aimed to assess the potential role of protein-modifying variants in endometriosis using exome-array genotyping in 7164 cases and 21005 controls, and a replication set of 1840 cases and 129016 controls of European ancestry. Results in the discovery sample identified significant evidence for association with coding variants in single-variant (rs1801232-CUBN) and gene-level (CIITA and PARP4) meta-analyses, but these did not survive replication. In the combined analysis, there was genome-wide significant evidence for rs13394619 (P = 2.3 × 10<sup>-9</sup>) in GREB1 at 2p25.1 - a locus previously identified in a GWA meta-analysis of European and Japanese samples. Despite sufficient power, our results did not identify any protein-modifying variants (MAF > 0.01) with moderate or large effect sizes in endometriosis, although these variants may exist in non-European populations or in high-risk families. The results suggest continued discovery efforts should focus on genotyping large numbers of surgically-confirmed endometriosis cases and controls, and/or sequencing high-risk families to identify novel rare variants to provide greater insights into the molecular pathogenesis of the disease.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | iPSYCH-SSI-Broad Group, Humans, Endometriosis, Genetic Predisposition to Disease, Case-Control Studies, Chromosome Mapping, Polymorphism, Single Nucleotide, Female, Meta-Analysis as Topic, Genetic Variation, Genome-Wide Association Study, Exome, Biomarkers, White People, Exome Sequencing |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 17 Oct 2017 13:02 |
| Last Modified: | 13 Feb 2023 23:30 |
| DOI: | 10.1038/s41598-017-10440-9 |
| Open Access URL: | http://www.nature.com/articles/s41598-017-10440-9 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3010296 |
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