In:
Scientific Reports, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2017-09-12)
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 −9 ) 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.
Type of Medium:
Online Resource
ISSN:
2045-2322
DOI:
10.1038/s41598-017-10440-9
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2017
detail.hit.zdb_id:
2615211-3