Browse
Submit Data
Databases
API
Help

Dataset Information

18 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Polycystic Ovary Syndrome Susceptibility Loci Inform Disease Etiological Heterogeneity.

ABSTRACT: Polycystic ovary syndrome (PCOS) is a complex disorder with heterogenous phenotypes and unclear etiology. A recent phenotypic clustering study identified metabolic and reproductive subtypes of PCOS. We hypothesize that the heterogeneity of PCOS manifestations reflects different mechanistic pathways and can be identified using a genetic approach. We applied k-means clustering to categorize the genome-wide significant PCOS variants into clusters based on their associations with selected quantitative traits that likely reflect PCOS etiological pathways. We evaluated the association of each cluster with PCOS-related traits and disease outcomes. We then applied Mendelian randomization to estimate the causal effects between the traits and PCOS. Three categories of variants were identified: adiposity, insulin resistant, and reproductive. Significant associations were observed for variants in the adiposity cluster with body mass index (BMI), waist circumference and breast cancer, and variants in the insulin-resistant cluster with fasting insulin, glucose values, and homeostatic model assessment of insulin resistance (HOMA-IR). Sex hormone binding globulin (SHBG) has strong association with all three clusters. Mendelian randomization suggested a causal role of BMI and SHBG on PCOS. No causal associations were observed for PCOS on disease outcomes.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC8234947 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Family-based analysis of eight susceptibility loci in polycystic ovary syndrome.

Project description:Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that is proposed to have a genetic basis. A recent genome-wide association study (GWAS) identified eight new risk loci that are independently associated with PCOS. To further validate the findings, a total of 321 case-parent trios (963 participants) who had a proband affected with PCOS were recruited for the family-based study. The transmission disequilibrium test (TDT) was used to analyze associations between PCOS and ten single nucleotide polymorphisms (SNPs) mapped to eight new susceptibility loci. Significant differences in transmission were observed for the SNPs rs2349415 (located in the FSHR gene, P?=?0.0001) and rs3802457 (located in the C9orf3 gene, P?=?0.0001), even after correction for multiple testing bias. The present data provides further evidence for an association between two susceptibility loci, 2p16.3 and 9q22.32, and PCOS. Follow-up functional studies on the FSHR and C9orf3 genes are required to understand their roles in PCOS development.

| S-EPMC4518258 | biostudies-literature

Prenatal androgen exposure and transgenerational susceptibility to polycystic ovary syndrome

Project description:The effects of how obesity and elevated androgen levels in women with polycystic ovary syndrome (PCOS) affect their offspring are unclear. We found that daughters of PCOS mothers are more likely to be diagnosed with PCOS in a Swedish nationwide register-based cohort and a clinical case-control study from Chile. Further, female mice (F0) with PCOS-like traits induced by late gestation injection of dihydrotestosterone, with and without obesity, produced female F1–F3 offspring with a PCOS-like reproductive and metabolic phenotypes. Sequencing of single MII oocytes from F1–F3 offspring revealed common and unique altered gene expression across all generations. Notably, four genes were also differentially expressed in serum samples from daughters in the case-control study and unrelated women with PCOS. Our findings provide evidence of transgenerational effects in female offspring of PCOS mothers and identify possible candidate genes for the prediction of a PCOS phenotype in future generations.

2019-10-30 | GSE133100 | GEO

RS1799817 in INSR associates with susceptibility to polycystic ovary syndrome.

Project description:Background:Insulin and its receptor (INSR) have been implicated in the etiology of the polycystic ovarian syndrome (PCOS). Here, we investigate the association between INSR rs1799817 polymorphism and PCOS in Saudi Arabian women. Methods:Study group included 126 PCOS women and 118 normo-ovulatory matched controls. The demographic data was recorded, and the plasma levels of glucose, lipids, leptin, E2, LH, FSH, T, SHBG, and insulin were determined. The genotypic and allele frequencies of rs1799817 were evaluated in both PCOS and control group. Polymerase chain reaction (PCR) was used to amplify Exon 17 of the INSR gene, and the amplified products were analyzed by direct sequencing. A single-nucleotide polymorphism (C to T) was found at locus 10923 (His1058) of rs1799817. Results:In the PCOS group, the mutant allele T occurs at a significantly higher frequency (0.306) compared to the control group (0.174) (p<0.001). It shows a dominant effect and elevates the relative risk of PCOS even in the heterozygotes (RR=2.82). After stratification of the participants by body mass index, the frequency of T allele was significantly higher in the lean patients with PCOS compared to the lean control. The obese PCOS also had a higher frequency than the obese control, but the difference was not statistically significant. Several parameter values were affected by the INSR genotype, particularly W/H ratio, lipid, insulin and glucose levels and insulin resistance in PCOS patients. Conclusions:The INSR gene polymorphism rs1799817 is a susceptibility locus associated with PCOS in Saudis and associated metabolic and hormonal changes, particularly, in the lean PCOS females.

| S-EPMC7526013 | biostudies-literature

Intergenerational associations of chronic disease and polycystic ovary syndrome.

Project description:BACKGROUND: Polycystic ovary syndrome (PCOS) is a common female endocrine disorder of heterogeneous clinical presentation, high disease burden, and unknown aetiology. The disease and associated conditions cluster in families, suggesting that PCOS may be the reproductive consequence of underlying chronic disease susceptibility. OBJECTIVE: To determine whether parents of young women with PCOS were more likely to have a history of diabetes or cardiovascular disease in later adult life. DESIGN, SETTING AND PARTICIPANTS: Structured interviews with 715 members of a cohort constructed by tracing female infants born at a single general hospital in Adelaide between 1973 and 1975. Participants were asked whether they had a pre-existing medical diagnosis of PCOS, and whether each parent had ever had high blood pressure, high cholesterol, diabetes, stroke, or heart disease. Maternal high blood pressure during pregnancy was taken from the medical record of the pregnancy with the study participant. RESULTS AND CONCLUSIONS: Mothers of women with PCOS were more likely than mothers of other women to have any cardiovascular disease (RR 1.78, 95% CI 1.29, 2.47), and nearly twice as likely to have high blood pressure (RR 1.95, 95% CI 1.38, 2.76). Fathers of women with PCOS were more than twice as likely to have heart disease (RR 2.36, 95% CI 1.44, 3.88) and over four times as likely to have had a stroke (RR 4.37, 95% CI 1.97, 9.70). Occurrence of cardiovascular disease in both mother and father are associated with the risk of PCOS in daughters. Further detailed study is required to elucidate the precise pathways that may be causally related to the observations.

| S-EPMC3186810 | biostudies-other

Relationship between the characteristic traits of polycystic ovary syndrome and susceptibility genes.

Project description:Polycystic ovary syndrome (PCOS) is a highly complex disorder influenced by genetic and environmental factors. Previous genome-wide association studies (GWAS) on Han Chinese, Korean, and European populations identified multiple PCOS-susceptible loci; however, only a few studies reported the association of susceptibility genes with disease phenotypic traits. This cross-sectional study aimed to investigate the association between PCOS susceptibility genes from GWAS and disease-related clinical features. A total of 1,810 reproductive-aged women were recruited, including 927 control women and 883 women with PCOS, diagnosed based on the European Society for Human Reproduction and Embryology criteria. Genomic DNA was extracted and genotyped, and a Bonferroni test was performed to determine the association between 12 independent SNPs and the clinical features of PCOS. In women with PCOS, rs11031006, nearest to FSHB, was significantly associated with free testosterone (P = 1.94 × 10-3) and luteinizing hormone (P = 1.96 × 10-3) levels. The menstruation number per year, ovarian follicular number, ovarian volume, and insulin sensitivity index were not associated with any SNP. In the control group, no SNPs were associated with any PCOS traits. Collectively, our results suggest that FSHB may play an important role in the development and progression of PCOS.

| S-EPMC7320020 | biostudies-literature

Polycystic Ovary Syndrome and Periodontal disease: Underlying Links- A Review.

Project description:Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age, which negatively affects various health systems. There is an extensive literature regarding the association of PCOS and other systemic conditions such as diabetes mellitus, cardiovascular disease, and psychological disorders. However, there is a lack of literature in associating PCOS and periodontal disease. Hence, PubMed search was done for various articles related to PCOS and its association with other comorbidities, including periodontal diseases. Analysis was done and data were synthesized and compiled in a sequential and presentable paradigm. This literature review of the pathophysiological mechanisms linking the two diseases suggests a positive relation between the two comorbidities. However, multicenter studies, with larger sample sizes, are to be conducted to establish a clearer and stronger association.

| S-EPMC5972486 | biostudies-other

Genetics of polycystic ovary syndrome.

Project description:The etiology of polycystic ovary syndrome (PCOS) has been difficult to determine because its features are heterogeneous, and its origin may also be heterogeneous. Twin studies suggest that its etiology is strongly heritable and genetic approaches are rapidly uncovering new regions of the genome that appear to confer risk for PCOS. Recent genome-wide association studies in Han Chinese women with PCOS demonstrate 11 genetic loci that are associated with PCOS. The variants identified are in regions that contain genes important for gonadotropin action, genes that are associated with risk for type 2 diabetes, and other genes in which the relationship to PCOS is not yet clear. Replication studies have demonstrated that variants at several of these loci also confer risk for PCOS in women of European ethnicity. The strongest loci in Europeans contain genes for DENND1A and THADA, with additional associations in loci containing the LHCGR and FSHR, YAP1 and RAB5/SUOX. The next steps in uncovering the pathophysiology borne out by these loci and variants will include mapping to determine the causal variant and gene, phenotype studies to determine whether these regions are associated with particular features of PCOS and functional studies of the causal variant to determine the direct cause of PCOS based on the underlying genetics. The next years will be very exciting times as groups from around the world come together to further elucidate the genetic origins of PCOS.

| S-EPMC4066994 | biostudies-literature

Obesity and polycystic ovary syndrome.

Project description:Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies in women of fertile age. Obesity is encountered in 30-70% of PCOS-affected women, and its presence significantly modifies both clinical and laboratory expression of the syndrome. Obesity increases the risk of co-morbidities associated with PCOS, such as impaired glucose tolerance and type 2 diabetes mellitus, hyperlipidemia and arterial hypertension. The etiopathogenesis of obesity in PCOS has not yet been exactly clarified. There clearly is a vicious circle of abdominal obesity, insulin resistance, and hyperadrogenemia. Differences in ghrelin and neuropeptide Y levels between PCOS patients and those with simple obesity were also described. Weight loss is the first choice recommendation for the treatment of clinical manifestations of PCOS, such as menstrual cycle irregularities, infertility or hirsutism. However, the best treatment approach in obese PCOS patients remains to be defined. Studies concerning different weight loss regimens, antiobesity drugs, bariatric surgery, insulin sensitizers, and hormonal therapy are reviewed.

| S-EPMC6444522 | biostudies-literature

PCOSDB: PolyCystic Ovary Syndrome Database for manually curated disease associated genes.

Project description:Polycystic ovary syndrome (PCOS) is a complex disorder affecting approximately 5-10 percent of all women of reproductive age. It is a multi-factorial endocrine disorder, which demonstrates menstrual disturbance, infertility, anovulation, hirsutism, hyper androgenism and others. It has been indicated that differential expression of genes, genetic level variations, and other molecular alterations interplay in PCOS and are the target sites for clinical applications. Therefore, integrating the PCOS-associated genes along with its alteration and underpinning the underlying mechanism might definitely provide valuable information to understand the disease mechanism. We manually curated the information from 234 published literatures, including gene, molecular alteration, details of association, significance of association, ethnicity, age, drug, and other annotated summaries. PCOSDB is an online resource that brings comprehensive information about the disease, and the implication of various genes and its mechanism. We present the curated information from peer reviewed literatures, and organized the information at various levels including differentially expressed genes in PCOS, genetic variations such as polymorphisms, mutations causing PCOS across various ethnicities. We have covered both significant and non-significant associations along with conflicting studies. PCOSDB v1.0 contains 208 gene reports, 427 molecular alterations, and 46 phenotypes associated with PCOS.

| S-EPMC4857457 | biostudies-other

Genetics of the polycystic ovary syndrome.

Project description:Polycystic ovary syndrome (PCOS) is a highly complex endocrine disorder, characterized by hyperandrogenemia, menstrual irregularities and polycystic ovaries. A strong genetic component to the etiology of PCOS is evident. However, due to the genetic and phenotypic heterogeneity of PCOS and the lack of insufficiently large cohorts, studies to identify specific contributing genes to date have yielded only few conclusive results. In this review we discuss the current status of the genetic analysis of PCOS including the results of numerous association studies with candidate genes involved in TGF-β and insulin signaling, type 2 diabetes mellitus and obesity susceptibility. Furthermore, we address current challenges in genetic studies of PCOS, and the promise of new approaches, including genome-wide association studies and next-generation sequencing.

| S-EPMC3609918 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data