Genetics Of Polycystic Ovary Syndrome Research Articles

An Update on the Genetics of Polycystic Ovary Syndrome

PCOS is a common endocrinopathy among women of reproductive age, with a worldwide prevalence of 8 to 13%, depending on the criteria used for diagnosis. It is characterized by a constellation of features, including oligo/anovulation, clinical and/or biochemical hyperandrogenism, and polycystic ovarian morphology. PCOS is one of the common causes of female infertility. It is also associated with metabolic derangements, including obesity, insulin resistance, and compensatory hyperinsulinemia, which increase the likelihood of developing type 2 diabetes mellitus. Despite extensive research, the etiology of PCOS remains largely unknown. It seems likely that the hypothalamic-pituitary-ovarian axis dysfunction, partial folliculogenesis arrest, insulin resistance, and ovarian and adrenal androgen secretion may play a role in the pathogenesis of PCOS. Familial clustering of the cases of PCOS points to a genetic component linked with it. The initial genetic studies suggest an autosomal dominant pattern of inheritance of the disorder in some families; however, most studies support multifactorial origin. Since PCOS is a complex trait, the typical form of inheritance of PCOS follows a non-Mendelian pattern and involves complex genetic mechanisms. Studies involving linkage and association have suggested a connection between genetic variations and the risk of developing PCOS in certain families or populations. Through genome-wide association studies and next-generation sequencing techniques, several candidate genes have been identified that play a role in the etiopathogenesis of the disorder. Pathogenic variants of various genes such as INSR, IRS1, GHRL, LDLR, MC4R, ADIPOQ, UCP1, UCP2, UCP3, FTO, PCSK9, FBN3, NEIL2, FDFT1, PCSK9, CYP11, CYP17, CYP21, HSD17, STAR, POR, AKR1C3, AMH, AMHR2, INHBA, AR, SHBG, LHR, FSHR, FSH β, SRD5A, GATA4, THADA, YAP1, ERBB2, DENND1A, FEM1B, FDFT1, NEIL2, TCF7L2, etc. in some PCOS cases are linked as underlying etiologic associations. This review aims to provide insight into the current genetic knowledge about PCOS. Discovering the genetic factors and pathways involved in the disorder will help us better comprehend the underlying mechanisms of the disorder.

Analyzing the Impact of FSHR Variants on Polycystic Ovary Syndrome-a Case-Control Study in Punjab.

Polycystic ovary syndrome (PCOS) is an endocrine-metabolic syndrome that involves hyperandrogenism, menstrual irregularities, and/or small cysts in one or both ovaries which might lead to infertility in women. The genetics of PCOS is heterogenous with the involvement of several genes reported in the hypothalamic-pituitary-gonadal axis. Follicular growth and steroidogenesis regulation are both critically dependent on follicle-stimulating hormone (FSH). The variants of FSHR cause abnormal folliculogenesis, steroidogenesis, and oocyte maturation at various stages of growth and may render women more susceptible to PCOS development. The present case-control study evaluated the association of FSHR rs6165 and rs6166 variants with PCOS. A total of 743 females were recruited. PCR-RFLP method was used for the genotypic analysis of FSHR polymorphisms. Obesity was examined according to the categorization of body mass index (BMI) and waist-hip ratio (WHR). Biochemical analysis, including a lipid profile, LH, FSH, and testosterone levels, was done in both PCOS women and controls. BMI and WHR revealed a statistically significant difference between PCOS cases and controls. Overall, levels of HDL were significantly lower, whereas cholesterol, triglycerides, LDL, and VLDL levels were higher in PCOS women (p < 0.05). The genotypic and allelic frequencies of rs6165 and rs6166 did not demonstrate significant differences when PCOS women were compared with the control group. However, clinical features of PCOS including gonadotropic hormone (FSH), hyperandrogenism, and dyslipidemia were significantly correlated with variants of FSHR. The present study concludes that rs6165 and rs6166 were significantly related to clinical features of PCOS, regardless of providing direct disease risk.

Current insights into the genetics of polycystic ovary syndrome

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

The Genetics of Polycystic Ovary Syndrome: An Overview of Candidate Gene Systematic Reviews and Genome-Wide Association Studies.

Polycystic Ovary Syndrome (PCOS) is a complex condition with mechanisms likely to involve the interaction between genetics and lifestyle. Familial clustering of PCOS symptoms is well documented, providing evidence for a genetic contribution to the condition. This overview aims firstly to systematically summarise the current literature surrounding genetics and PCOS, and secondly, to assess the methodological quality of current systematic reviews and identify limitations. Four databases were searched to identify candidate gene systematic reviews, and quality was assessed with the AMSTAR tool. Genome-wide association studies (GWAS) were identified by a semi structured literature search. Of the candidate gene systematic reviews, 17 were of high to moderate quality and four were of low quality. A total of 19 gene loci have been associated with risk of PCOS in GWAS, and 11 of these have been replicated across two different ancestries. Gene loci were located in the neuroendocrine, metabolic, and reproductive pathways. Overall, the gene loci with the most robust findings were THADA, FSHR, INS-VNTR, and DENND1A, that now require validation. This overview also identified limitations of the current literature and important methodological considerations for future genetic studies. Much work remains to identify causal variants and functional relevance of genes associated with PCOS.

Female Genomics: Infertility and Overall Health.

AbstractFemale infertility is a complex disease linked to multiple etiologies including genetic factors. Owing to the multifactorial nature of infertility, it is often difficult to identify single causative genes. Despite this challenge, investigations into the genetic causes of infertility have been performed to shed light on the etiology and for the possibility of developing personalized medical approaches to therapy. Multiple techniques have been utilized to better characterize the genetic origins of this disease, including genome-wide association studies. We present here a review of the genetic causes of female infertility, detailing some of the more recent findings in the genetics of polycystic ovary syndrome, endometriosis, primary ovarian insufficiency, hypothalamic amenorrhea, leiomyomas, and Mullerian anomalies.

Genetics of PCOS: A systematic bioinformatics approach to unveil the proteins responsible for PCOS

Polycystic ovary syndrome (PCOS) is a hormonal imbalance in women, which causes problems during menstrual cycle and in pregnancy that sometimes results in fatality. Though the genetics of PCOS is not fully understood, early diagnosis and treatment can prevent long-term effects. In this study, we have studied the proteins involved in PCOS and the structural aspects of the proteins that are taken into consideration using computational tools. The proteins involved are modeled using Modeller 9v14 and Ab-initio programs. All the 43 proteins responsible for PCOS were subjected to phylogenetic analysis to identify the relatedness of the proteins. Further, microarray data analysis of PCOS datasets was analyzed that was downloaded from GEO datasets to find the significant protein-coding genes responsible for PCOS, which is an addition to the reported protein-coding genes. Various statistical analyses were done using R programming to get an insight into the structural aspects of PCOS that can be used as drug targets to treat PCOS and other related reproductive diseases.

PCOS in 2015: New insights into the genetics of polycystic ovary syndrome.

PCOS in 2015: New insights into the genetics of polycystic ovary syndrome.

Molecular Genetics of Polycystic Ovary Syndrome: An Update

Polycystic ovary syndrome (PCOS) is a complex genetic disorder caused by interplay between several 'susceptibility' genes and environment factors. In the past few years, numerous studies of genomics and transcriptomics attempted to discover genes affecting PCOS. Pre-genome wide association study (GWAS) plays a stepping stone effect on the progress of PCOS, even though most of the strongest associations are for loci rather than functional variants. A trend towards large-scale GWAS has succeeded in identifying many additional novel PCOS loci. Most of the PCOS-associated regions are shared with other diseases or symptoms, as well as with metabolism, inflammation or insulin signaling-related traits, or cancer. Moreover, susceptibility genes for early diagnosis of PCOS are expected to offer the prevention of long-term risk of obesity, cardiovascular disease, and type 2 diabetes (T2DM) as well. Furthermore, considerable advanced new technical approaches such as GWAS and next-generation sequencing will provide new opportunities in the molecular analysis of PCOS, which can, in the long term, lead to new therapeutic treatments for the disorder. The present review discusses heterogeneous clinical manifestations of PCOS, controversies surrounding the diagnosis of PCOS, and the recent findings of pre-GWAS and GWAS studies on PCOS, highlighting the relevant candidate gene families and their potential functional pathways relevant for PCOS.

Genetic basis of polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is associated with obesity and manifests with reproductive, hyperandrogenic and metabolic features. Although the etiology of PCOS is complex and incompletely understood, genetics plays an important role (heritability: ∼70%). Potential problems with studying the genetics of PCOS include the heterogeneity of the condition and associated sub-fertility. A candidate gene approach has been used in over 70 published studies on PCOS, most of which have been inadequately powered to detect a statistically meaningful association. Furthermore, these studies often fail to replicate prior published studies on the same candidate gene in different populations. The first genome-sequence variant (identified from a genome-wide association study in subjects with Type 2 diabetes mellitus) to be studied in PCOS (FTO gene) has been shown by our group to associate with susceptibility for the development of PCOS. This is the first genetic corroboration of a link between PCOS and obesity. Future directions include a genome-wide association study in PCOS.

Family size in women with polycystic ovary syndrome

Given that polycystic ovary syndrome (PCOS) is associated with oligo-ovulatory infertility and is an inherited trait, we hypothesized that the families of patients with PCOS are smaller than those of matched controls. However, our study of 106 white patients with PCOS, ages 18-45, and 53 healthy eumenorrheic nonhirsute white controls did not indicate a difference in family size between the groups; these results have important implications for the design of prospective studies of the heritability and genetics of PCOS.

The genetics of polycystic ovary syndrome

The genetics of polycystic ovary syndrome

Genetics of polycystic ovary syndrome: searching for the way out of the labyrinth

Polycystic ovary syndrome (PCOS) is a complex and heterogeneous disorder presenting a challenge for clinical investigators. It is the most common endocrine disorder of women in reproductive age, a multifaceted reproductive, cosmetic and metabolic problem, with an enigmatic pathophysiological and molecular basis. Although the familial segregation has been noticed very early in the description of the syndrome and family studies in first-degree relatives of women diagnosed with PCOS reveal clustering of the disease, the genetic studies have not as yet determine the pattern of heredity. Part of the problem in genetic studies has been the lack of uniform criteria for diagnosis, heterogeneity of phenotypic features and the fact that the disorder is only expressed clinically in women during their reproductive years. Even within affected families and between sisters with polycystic ovaries, there is heterogeneity in presentation. However, regardless of diagnostic criteria used to identify profanes and to determine affected status in the kindred, the foundation of genetic studies suggests a strong familial component. Currently, PCOS is considered a polygenic trait that might result from the interaction of susceptible and protective genomic variants under the influence of environmental factors, whose role is under intensive investigation. Candidate genes cover a broad spectrum of an endless list of molecules which participate on every step of reproductive and metabolic pathways of this syndrome. Focused research in identification of these genes may provide valuable information and shed some light on the way out of the genomic labyrinth, elucidating the underlying pathophysiology and aiming at a more efficient therapeutic approach of this complicated endocrine disorder.

Candidate genes in polycystic ovary syndrome.

The candidate gene approach has already paid some dividends in trying to understand the complex genetics of polycystic ovary syndrome (PCOS). In terms of steroidogenic abnormalities, CYP11a-encoding P450 side chain cleavage-appears to be a major susceptibility locus. In relation to the well-described metabolic disturbances in PCOS, the insulin gene variable number tandem repeat (VNTR) appears to be a promising candidate, at least in populations studied in the UK. Finally, genes implicated in ovarian follicular development may have a role in the aetiology of PCOS, as demonstrated by recent identification of the follistatin gene as a potential disease locus. It seems unlikely that PCOS can be explained on the basis of a single gene disorder although, in a given family, one gene may have a predominant effect. An oligogenic model seems the most appropriate basis on which to understand the genetic origins of this very common disorder. The candidate gene approach has been useful to date, but it may prove important in the near future to perform an anonymous genome-wide scan to identify hitherto unheralded susceptibility loci.

Genetics of polycystic ovary syndrome

International Journal of Gynecology & ObstetricsVolume 70, Issue S3 p. C10-C10 Invited presentation polycystic ovarian diseases Genetics of polycystic ovary syndrome Stephen Franks, Stephen FranksSearch for more papers by this author Stephen Franks, Stephen FranksSearch for more papers by this author First published: 10 December 2003 https://doi.org/10.1016/S0020-7292(00)81418-6AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume70, IssueS32000Pages C10-C10 RelatedInformation

Genetics of polycystic ovary syndrome

We have found evidence for the involvement of two major genes in the aetiology of PCOS. The results of both linkage and association studies suggest that CYP11a (coding for P450 cholesterol side chain cleavage) and the insulin VNTR regulatory polymorphism are important genes in the aetiology of PCOS and may explain, in part, the heterogeneity of the syndrome. Differences in expression of CYP11a could account for variation in androgen production in women who have polycystic ovaries and those subjects who are homozygous for III alleles at the insulin gene VNTR locus are more likely to be hyperinsulinaemic. It is likely that other genes are involved in the aetiology of PCOS. Recent results lend weight to the idea that PCOS represents a complex trait in which several genes—but perhaps a relatively small number of key genes—contribute, in conjunction with nutritional factors, to the observed clinical and biochemical heterogeneity.

The genetics of polycystic ovary syndrome

Problems that confound the clinical characterization of polycystic ovary syndrome (PCOS) also complicate the search for its genetic cause. There is no consensus as to the nature of the clinical phenotype for PCOS, and there is even doubt whether polycystic ovaries are an indispensable part of the syndrome. Few ethnic studies on PCOS have been performed, although it has been reported in most major racial groups. Genetic studies of family clusters and relatives of affective probands have shown a high incidence of affected relatives. A dominant mode of inheritance, rather than a recessive one, seems more likely. Multiple genetic causes of adult-onset hyperandrogenism and chronic anovulation have been identified. Chromosomal studies of patients with PCOS have shown no consistent abnormality. Molecular genetic studies are now ongoing. Future genetic models should consider such problematic areas as the heterogeneity of the syndrome, phenotypes in males as well as in females in the nonreproductive years, the exclusion of secondary causes of hyperandrogenism, and the persistence of a syndrome that adversely affects fecundity.