Systematic review of genome-wide association studies on susceptibility to endometriosis

Cardoso, Jéssica Vilarinho; Perini, Jamila Alessandra; Machado, Daniel Escorsim; Pinto, Ricardo; Medeiros, Rui

doi:10.1016/j.ejogrb.2020.10.017

“…The study, which is a systematic review of GWAS studies published by PubMed until December 31, 2019, indicates that variants of the genes WNT4 rs7521902, GREB1 rs13394619, FN1 rs1250248, IL1A rs6542095 and VEZT rs10859871 may affect the development of endometriosis. However, replication and validation of these variants in different populations are essential for a better understanding of endometriosis etiopathogenesis, to optimize diagnosis, and to improve the effectiveness of clinical treatment of the disease [ 196 ].…”

Section: Endometriosis—geneticsmentioning

confidence: 99%

Endometriosis: Epidemiology, Classification, Pathogenesis, Treatment and Genetics (Review of Literature)

Smolarz

¹

,

Szyłło

²

,

Romanowicz

³

2021

IJMS

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Endometriosis is a “mysterious” disease and its exact cause has not yet been established. Among the etiological factors, congenital, environmental, epigenetic, autoimmune and allergic factors are listed. It is believed that the primary mechanism of the formation of endometriosis foci is retrograde menstruation, i.e., the passage of menstrual blood through the fallopian tubes into the peritoneal cavity and implantation of exfoliated endometrial cells. However, since this mechanism is also observed in healthy women, other factors must also be involved in the formation of endometriosis foci. Endometriosis is in many women the cause of infertility, chronic pain and the deterioration of the quality of life. It also represents a significant financial burden on health systems. The article presents a review of the literature on endometriosis—a disease affecting women throughout the world.

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“…The sample size of the present study is calculated taking into consideration the expected effect sizes for genetic risk factors, the possibility for discovery of population-specific risk factors, selection criteria for cases and controls, and differences in allelic frequencies among studied populations. 26 …”

Section: Methods and Analysismentioning

confidence: 99%

Protocol for a case–control study investigating the clinical phenotypes and genetic regulation of endometriosis in Indian women: the ECGRI study

Gajbhiye

¹

,

Montgomery

²

,

Pai

³

et al. 2021

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Introduction Endometriosis is one of the common, gynaecological disorders associated with chronic pelvic pain and subfertility affecting ~10% of reproductive age women. The clinical presentation, etiopathogenesis of endometriosis subtypes and associated risk factors are largely unknown. Genome-Wide Association (GWA) Studies (GWAS) provide strong evidence for the role of genetic risk factors contributing to endometriosis. However, no studies have investigated the association of the GWAS-identified single-nucleotide polymorphism (SNPs) with endometriosis risk in the Indian population; therefore, one-sixth of the world’s population is not represented in the global genome consortiums on endometriosis. The Endometriosis Clinical and Genetic Research in India (ECGRI) study aims to broaden our understanding of the clinical phenotypes and genetic risks associated with endometriosis. Methods and analysis ECGRI is a large-scale, multisite, case–control study of 2000 endometriosis cases and 2000 hospital controls to be recruited over 4 years at 15 collaborating study sites across India covering representative Indian population from east,north-east, north, central, west and southern geographical zones of India. We will use the World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonisation Project (WERF-EPHect) data collection instruments for capturing information on clinical, epidemiological, lifestyle, environmental and surgical factors. WERF-EPHect standard operating procedures will be followed for the collection, processing and storage of biological samples. The principal analyses will be for main outcome measures of the incidence of endometriosis, disease subtypes and disease severity determined from the clinical data. This will be followed by GWAS within and across ethnic groups. Ethics and dissemination The study is approved by the Institutional Ethics Committee of Indian Council of Medical Research-National Institute for Research in Reproductive Health and all participating study sites. The study is also approved by the Health Ministry Screening Committee of the Government of India. The results from this study will be actively disseminated through discussions with endometriosis patient groups, conference presentations and published manuscripts.

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“…The 10 most robust SNPs found from the different large GWAS in endometriosis have been described and discussed in detail in 2020 [ 49 ]; here we present an additional discussion of these studies. The first large-scale GWAS on endometriosis was carried out in 2010 in Japan [ 30 ].…”

Section: Genome-wide Association Studiesmentioning

confidence: 99%

Genomics of Endometriosis: From Genome Wide Association Studies to Exome Sequencing

Lalami

¹

,

Abo

²

,

Borghese

³

et al. 2021

IJMS

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This review aims at better understanding the genetics of endometriosis. Endometriosis is a frequent feminine disease, affecting up to 10% of women, and characterized by pain and infertility. In the most accepted hypothesis, endometriosis is caused by the implantation of uterine tissue at ectopic abdominal places, originating from retrograde menses. Despite the obvious genetic complexity of the disease, analysis of sibs has allowed heritability estimation of endometriosis at ~50%. From 2010, large Genome Wide Association Studies (GWAS), aimed at identifying the genes and loci underlying this genetic determinism. Some of these loci were confirmed in other populations and replication studies, some new loci were also found through meta-analyses using pooled samples. For two loci on chromosomes 1 (near CCD42) and chromosome 9 (near CDKN2A), functional explanations of the SNP (Single Nucleotide Polymorphism) effects have been more thoroughly studied. While a handful of chromosome regions and genes have clearly been identified and statistically demonstrated as at-risk for the disease, only a small part of the heritability is explained (missing heritability). Some attempts of exome sequencing started to identify additional genes from families or populations, but are still scarce. The solution may reside inside a combined effort: increasing the size of the GWAS designs, better categorize the clinical forms of the disease before analyzing genome-wide polymorphisms, and generalizing exome sequencing ventures. We try here to provide a vision of what we have and what we should obtain to completely elucidate the genetics of this complex disease.

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Systematic review of genome-wide association studies on susceptibility to endometriosis

Cited by 20 publications

References 41 publications

Endometriosis: Epidemiology, Classification, Pathogenesis, Treatment and Genetics (Review of Literature)

Endometriosis: Epidemiology, Classification, Pathogenesis, Treatment and Genetics (Review of Literature)

Protocol for a case–control study investigating the clinical phenotypes and genetic regulation of endometriosis in Indian women: the ECGRI study

Genomics of Endometriosis: From Genome Wide Association Studies to Exome Sequencing

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