Independent replication and meta-analysis for endometriosis risk loci

Endometriosis is a complex disease that affects 6-10% of women in their reproductive years and 20-50% of women with infertility. Genome-wide and candidate-gene association studies for endometriosis have identified 10 independent risk loci, and of these, nine (rs7521902, rs13394619, rs4141819, rs6542095, rs1519761, rs7739264, rs12700667, rs1537377, and rs10859871) are polymorphic in European populations. Here we investigate the replication of nine SNP loci in 998 laparoscopically and histologically confirmed endometriosis cases and 783 disease-free controls from Belgium. SNPs rs7521902, rs13394... Mehr ...

Verfasser: Sapkota, Yadav
Fassbender, Amelie
Bowdler, Lisa
Fung, Jenny
Peterse, Danielle
O, Dorien
Montgomery, Grant
Nyholt, Dale
D'Hooghe, Thomas
Dokumenttyp: Contribution to Journal
Erscheinungsdatum: 2015
Verlag/Hrsg.: Cambridge University Press
Schlagwörter: Article / Belgium / CDKN2B AS1 gene / European / GREB1 gene / ID4 gene / IL1A / IL1A gene / VEZT gene / Wnt4 protein / accuracy / chromosome 12q / chromosome 1p / chromosome 2p / chromosome 6p / chromosome 7p / chromosome 9p / cohort analysis / comparative study / disease severity / effect size / endometriosis / gene / gene frequency / gene locus / genetic association / genetic risk / genetic variability / genome-wide association study / haplotype / human / interleukin 1alpha / meta-analysis / priority journal / publication / quality control / replication / replication study / single nucleotide polymorphism
Sprache: unknown
Permalink: https://search.fid-benelux.de/Record/base-26978068
Datenquelle: BASE; Originalkatalog
Powered By: BASE
Link(s) : https://eprints.qut.edu.au/91747/

Endometriosis is a complex disease that affects 6-10% of women in their reproductive years and 20-50% of women with infertility. Genome-wide and candidate-gene association studies for endometriosis have identified 10 independent risk loci, and of these, nine (rs7521902, rs13394619, rs4141819, rs6542095, rs1519761, rs7739264, rs12700667, rs1537377, and rs10859871) are polymorphic in European populations. Here we investigate the replication of nine SNP loci in 998 laparoscopically and histologically confirmed endometriosis cases and 783 disease-free controls from Belgium. SNPs rs7521902, rs13394619, and rs6542095 show nominally significant (p <.05) associations with endometriosis, while the directions of effect for seven SNPs are consistent with the original reports. Association of rs6542095 at the IL1A locus with 'All' (p =.066) and 'Grade-B' (p =.01) endometriosis is noteworthy because this is the first successful replication in an independent population. Meta-analysis with the published results yields genome-wide significant evidence for rs7521902, rs13394619, rs6542095, rs12700667, rs7739264, and rs1537377. Notably, three coding variants in GREB1 (near rs13394619) and CDKN2B-AS1 (near rs1537377) also showed nominally significant associations with endometriosis. Overall, this study provides important replication in a uniquely characterized independent population, and indicates that the majority of the original genome-wide association findings are not due to chance alone.