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.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1017/thg.2015.61 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Systematic review of genome-wide association studies on susceptibility to endometriosis.
Eur J Obstet Gynecol Reprod Biol
December 2020
Molecular Oncology Group-CI, Portuguese Institute of Oncology, Porto, Portugal.
Endometriosis is a complex and heterogeneous disease in which extrinsic and intrinsic factors, such as genetics, provide to the disease development. Genome-wide association (GWA) studies may be essential to recognize genetic variants associated with the endometriosis risk. However, in the current literature there are some conflicting results between these studies.
View Article and Find Full Text PDFThe assessment of GWAS - identified polymorphisms associated with infertility risk in Polish women with endometriosis.
Ginekol Pol
November 2018
Department of Biochemistry and Molecular Biology University of Medical Sciences Karol Marcinkowski, 6 Święcickiego, 60-781 Poznań, Poland.
Objectives: Genome-wide association studies in patients with endometriosis revealed ten significant single nucleo-tide polymorphisms (SNPs) in the Caucasian population, which include rs12700667 near NFE2L3, rs12037376 in WNT4, rs7521902 near WNT4, rs13394619 in GREB1, rs10859871 near VEZT, rs1537377 near CDKN2B-AS1, rs4141819 near ETAA1, rs7739264 near ID4, rs1519761 near RND3 and rs6542095 near IL1A.
Material And Methods: We replicated ten polymorphisms among infertile women with endometriosis (n = 315) and healthy fertile women (n = 406) in the Polish Caucasian population. Genotyping was conducted either by high-resolution melting curve analysis or by a pre-designed TaqMan probe.
Independent Replication and Meta-Analysis for Endometriosis Risk Loci.
Twin Res Hum Genet
October 2015
Department of Development and Regeneration,Organ Systems,KU Leuven,Leuven,Belgium.
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.
View Article and Find Full Text PDFReplication and meta-analysis of previous genome-wide association studies confirm vezatin as the locus with the strongest evidence for association with endometriosis.
Hum Reprod
April 2015
Molecular Biology Laboratory, Istituto Auxologico Italiano, Milano, Italy.
Study Question: Is it possible to replicate the genetic association of single nucleotide polymorphisms (SNPs) rs13394619, rs4141819, rs7739264, rs17694933 and rs10859871 in five genetic loci previously identified as associated with endometriosis in an Italian Caucasian population?
Summary Answer: SNP rs10859871 near the vezatin (VEZT) gene was found to be significantly associated with endometriosis in general while SNPs rs17694933 and rs4141819 were associated with Stage III/IV and ovarian disease, respectively.
What Is Known Already: Endometriosis represents a complex disease in which the phenotypic manifestations are influenced by both genetic and environmental factors. Recent genome-wide association studies (GWASs) have allowed to identify some SNPs associated with the predisposition to the disease.
Genetic variants underlying risk of endometriosis: insights from meta-analysis of eight genome-wide association and replication datasets.
Hum Reprod Update
October 2014
Wellcome Trust Center for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK.
Background: Endometriosis is a heritable common gynaecological condition influenced by multiple genetic and environmental factors. Genome-wide association studies (GWASs) have proved successful in identifying common genetic variants of moderate effects for various complex diseases. To date, eight GWAS and replication studies from multiple populations have been published on endometriosis.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!