A5019988195- Ovarian function and disorders
- Reproductive Biology and Fertility
- Sexual Differentiation and Disorders
- Hormonal and reproductive studies
- Genetic Associations and Epidemiology
- Birth, Development, and Health
- Genetic and phenotypic traits in livestock
- Genetic Mapping and Diversity in Plants and Animals
- Advanced Chemical Sensor Technologies
- Analytical Chemistry and Chromatography
- Sperm and Testicular Function
- Advanced Computing and Algorithms
- Nutrition, Genetics, and Disease
- Single-cell and spatial transcriptomics
- Ovarian cancer diagnosis and treatment
- Estrogen and related hormone effects
- Folate and B Vitamins Research
- Electrolyte and hormonal disorders
- Atherosclerosis and Cardiovascular Diseases
- Blood transfusion and management
- Microbial Inactivation Methods
- Genetic Syndromes and Imprinting
- Growth Hormone and Insulin-like Growth Factors
- Cardiovascular Disease and Adiposity
- Erythropoietin and Anemia Treatment
Northwestern University
2015-2024
Polycystic ovary syndrome (PCOS) is a common, highly heritable complex disorder of unknown aetiology characterized by hyperandrogenism, chronic anovulation and defects in glucose homeostasis. Increased luteinizing hormone relative to follicle-stimulating secretion, insulin resistance developmental exposure androgens are hypothesized play causal role PCOS. Here we map common genetic susceptibility loci European ancestry women for the National Institutes Health PCOS phenotype, which confers...
Background Polycystic ovary syndrome (PCOS) is a common, complex genetic disorder affecting up to 15% of reproductive-age women worldwide, depending on the diagnostic criteria applied. These are based expert opinion and have been subject considerable controversy. The phenotypic variation observed in PCOS suggestive an underlying heterogeneity, but recent meta-analysis European ancestry cases found that architecture defined by different was generally similar, suggesting do not identify...
Polycystic ovary syndrome (PCOS), a common endocrine condition, is the leading cause of anovulatory infertility.Given that disease-susceptibility variants account for only small percentage estimated PCOS heritability, we tested hypothesis rare contribute to this deficit in heritability.Unbiased whole-genome sequencing (WGS) 80 patients with and 24 reproductively normal control subjects identified potentially deleterious AMH, gene encoding anti-Müllerian hormone (AMH). Targeted AMH 643 153...
Polycystic ovary syndrome (PCOS) is among the most common endocrine disorders of premenopausal women, affecting 5% to15% this population depending on diagnostic criteria applied. It characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology. PCOS highly heritable, but only a small proportion heritability can be accounted for genetic susceptibility variants identified to date.
Femoral atherosclerotic plaques are less inflammatory than carotid histologically, but limited cell-level data exist regarding comparative immune landscapes and polarization at these sites. We investigated intraplaque leukocyte phenotypes transcriptional in 49 patients undergoing femoral (n = 23) or 26) endarterectomy using single-cell RNA-Seq (scRNA-Seq; n 13), flow cytometry 24), IHC 12). Comparative scRNA-Seq of CD45+-selected leukocytes from 9; 35,265 cells) 4; 30,655 plaque revealed...
Polycystic ovary syndrome (PCOS) and its underlying features remain poorly understood. In this genetic proteomic study, we expand the number of loci from 19 to 29, identify 31 associated plasma proteins. Many risk-increasing were with later age at menopause, underscoring reproductive longevity related a larger functional ovarian reserve. Hormonal regulation in aetiology condition, through metabolic features, was emphasised. The analysis highlighted perturbations metabolically-related biology...
Abstract Context Hierarchical clustering (HC) identifies subtypes of polycystic ovary syndrome (PCOS). Objective This work aimed to identify clinically significant in a PCOS cohort diagnosed with the Rotterdam criteria and further characterize distinct subtypes. Methods Clustering was performed using variables body mass index (BMI), luteinizing hormone (LH), follicle-stimulating hormone, dehydroepiandrosterone sulfate, sex hormone–binding globulin (SHBG), testosterone, insulin, glucose....
Abstract Context Hyperandrogenemia (HA) is a consistent reproductive phenotype in women with polycystic ovary syndrome (PCOS) and their relatives. Increased testosterone levels are present premenarchal daughters of affected (PCOS-d). Obese girls (OB-g) without family history PCOS also have peripubertal HA. The sources significance HA these groups remains unknown. Objective 11-oxygenated 19-carbon (C19) steroids adrenally derived androgens that elevated hyperandrogenic disorders, including...
Polycystic ovary syndrome (PCOS) is a highly heritable complex trait. Parents of affected women have reproductive and metabolic phenotypes.We tested the hypothesis that there are parental effects on heritability fasting dysglycemia in with PCOS.This was cross-sectional study at an academic medical center.PARTICIPANTS included 367 PCOS their parents (1101 total subjects).We compared maternal paternal contributions to transmission susceptibility allele D19S884 within fibrillin-3 gene...
Women with metabolic syndrome (MetS) have higher endogenous testosterone (T) levels than unaffected women. This study investigated whether hyperandrogenemia (HA) was a marker for increased cardiometabolic risk in reproductively normal premenopausal women.Reproductive hormones and parameters were assessed 198 women regular menses no clinical hyperandrogenism (eumenorrheic [EM]). Hyperandrogenic EM compared 110 NIH criteria polycystic ovary syndrome.Twenty-two percent of had HA. Levels non-sex...
11-oxygenated C19 steroids (11-oxyandrogens) have been shown to rise during adrenarche and remain higher throughout adulthood than in early childhood. The patterns of circulating 11-oxyandrogens normal puberty not yet described.
Abstract Polycystic ovary syndrome (PCOS) is among the most common disorders affecting up to 15% of menstruating population globally. It leading cause anovulatory infertility and a major risk factor for type 2 diabetes. Elevated testosterone levels are core endophenotype. Despite that prevalence, underlying causes remain unknown. PCOS genome-wide association studies (GWAS) have reproducibly mapped number susceptibility loci, including one encompassing gene regulating androgen biosynthesis,...
Abstract Disclosure: K. Brewer: None. R. Sisk: M. Dapas: C. Li: A. Dunaif: Consulting Fee; Self; AcaciaBio, Inc, Neurocine Biosciences, Inc. Speaker; Quest Diagnostics. Other; Co-Editor Endocrine Today, Healio, Slack Clustering methods have been used to resolve heterogeneity within complex diseases elucidate underlying biologic mechanisms. We (Dapas et al. PLoS Med, 2020) and others applied these PCOS identified discrete subtypes, including those that capture distinct reproductive or...
Abstract Disclosure: K. Brewer: None. R. Sisk: M. Dapas: C. Li: A. Dunaif: Consulting Fee; Self; AcaciaBio, Inc, Neurocine Biosciences, Inc. Speaker; Quest Diagnostics. Other; Co-Editor Endocrine Today, Healio, Slack Clustering methods have been used to resolve heterogeneity within complex diseases elucidate underlying biologic mechanisms. We (Dapas et al. PLoS Med, 2020) and others applied these PCOS identified discrete subtypes, including those that capture distinct reproductive or...
Abstract Disclosure: K. van der Ham: None. L.M. Moolhuijsen: Brewer: R. Sisk: Y.V. Louwers: J.A. Visser: A.E. Dunaif: J.S. Laven: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive-age. The different criteria that are used to diagnose PCOS reflect the heterogeneity syndrome. However, diagnosed by NIH or Rotterdam have similar genetic architecture. Using Hierarchical Clustering (HC) cohort ∼900 cases from European ancestry, we previously identified...
Abstract Disclosure: K. Brewer: None. R. Sisk: H. Lee: L.M. Moolhuijsen: van der Ham: Y. Louwers: J.A. Visser: M. Dapas: S. Franks: J.S. Laven: C. Li: A.E. Dunaif: The phenotypic variation observed in PCOS is suggestive of underlying genetic heterogeneity, but a recent meta-analysis European ancestry (EA) cases found that the architecture defined by NIH and Rotterdam diagnostic criteria was similar, suggesting these do not identify biologically distinct disease phenotypes. Using Hierarchical...
Abstract PCOS diagnosed by NIH or non-NIH Rotterdam criteria self-report is generally genetically similar. Using Hierarchical Clustering (HC), we have previously identified discrete, stable subtypes, which designated reproductive (higher LH, FSH, SHBG) and metabolic BMI, insulin, glucose), in a United States (US) cohort of ∼900 (Dapas et al. PLoS Med, 2020). The subtypes appeared to capture biologically meaningful differences because they were associated with distinct novel genome-wide...
ABSTRACT Polycystic ovary syndrome (PCOS) is among the most common endocrine disorders of premenopausal women, affecting 5-15% this population depending on diagnostic criteria applied. It characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology. PCOS a leading risk factor for type 2 diabetes in young women. highly heritable, but only small proportion heritability can be accounted genetic susceptibility variants identified to date. To test hypothesis that...
Abstract Background Polycystic ovary syndrome (PCOS) is a common, complex genetic disorder affecting up to 15% of reproductive age women worldwide, depending on the diagnostic criteria applied. These are based expert opinion and have been subject considerable controversy. The phenotypic variation observed in PCOS suggestive an underlying heterogeneity, but recent meta-analysis European ancestry cases found that architecture defined by different was generally similar, suggesting do not...
Abstract Study question Does unsupervised clustering identify biologically distinct subtypes in a cohort of women with polycystic ovary syndrome (PCOS) diagnosed by Rotterdam criteria? Summary answer This study demonstrates that hierarchical eight pre-defined quantitative reproductive and metabolic traits identifies PCOS. What is known already PCOS common, heterogeneous, endocrine disorder reproductive-age. NIH or non-NIH criteria self-report generally genetically similar. Using Hierarchical...
Abstract Disclosure: J. Cai: None. K. Brewer: R. Sisk: R.S. Legro: A.E. Dunaif: Prenatal exposure to androgens produces phenocopies of PCOS in animal models. In mice, there is evidence for transgenerational prenatal androgen effects. Human studies considered support the hypothesis that intrauterine actions play a major role pathogenesis come from (1) health registries where mothers and daughters was diagnosed by ICD codes (2) retrospective assessment mother’s status cohorts affected women....