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Analysis of potential protein-modifying variants in 9000 endometriosis patients and 150000 controls of European ancestry

Analysis of potential protein-modifying variants in 9000 endometriosis patients and 150000 controls of European ancestry


Titill: Analysis of potential protein-modifying variants in 9000 endometriosis patients and 150000 controls of European ancestry
Höfundur: Sapkota, Yadav
De Vivo, Immaculata
Steinthorsdottir, Valgerdur   orcid.org/0000-0003-1846-6274
Fassbender, Amelie
Bowdler, Lisa
Buring, Julie E.
Edwards, Todd L.
Jones, Sarah
Dorien, O.
Peterse, Danielle
... 15 fleiri höfundar Sýna alla höfunda
Útgáfa: 2017-09
Tungumál: Enska
Umfang: 11380
Háskóli/Stofnun: Háskóli Íslands
University of Iceland
Svið: Heilbrigðisvísindasvið (HÍ)
School of Health Sciences (UI)
Deild: Læknadeild (HÍ)
Faculty of Medicine (UI)
Birtist í: Scientific Reports;7
ISSN: 2045-2322
DOI: 10.1038/s41598-017-10440-9
Efnisorð: Genetic markers; Genome-wide association studies; Legslímuflakk; Erfðafræði; Rannsóknir
URI: https://hdl.handle.net/20.500.11815/555

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Tilvitnun:

Sapkota, Y., Vivo, I. D., Steinthorsdottir, V., Fassbender, A., Bowdler, L., Buring, J. E., . . . Montgomery, G. W. (2017). Analysis of potential protein-modifying variants in 9000 endometriosis patients and 150000 controls of European ancestry. Scientific Reports, 7(1), 11380. doi:10.1038/s41598-017-10440-9

Útdráttur:

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.

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