scholarly journals Sex Modifies the Effect of Genetic Risk Scores for Polycystic Ovary Syndrome on Metabolic Phenotypes

2021 ◽  
Author(s):  
Ky'Era V. Actkins ◽  
Genevieve Jean-Pierre ◽  
Melinda C. Aldrich ◽  
Digna R. Velez Edwards ◽  
Lea K. Davis
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Genetic Risk ◽  
Polycystic Ovary ◽  
Medical Center ◽  
Genetic Risk Score ◽  
Risk Scores ◽  
Ovary Syndrome ◽  
Biological Variables ◽  
Increased Risk ◽  
The Relationship

Females with polycystic ovary syndrome (PCOS), the most common endocrine disorder in women, have an increased risk of developing metabolic disorders such as insulin resistance, obesity, and type 2 diabetes (T2D). Furthermore, while only diagnosable in females, males with a family history of PCOS can also exhibit a poor cardiometabolic profile. Therefore, we aimed to elucidate the role of sex in the relationship between PCOS and its comorbidities by conducting bidirectional genetic risk score analyses in both sexes. We conducted a phenome-wide association study (PheWAS) using PCOS polygenic risk scores (PCOSPRS) to understand the pleiotropic effects of PCOS genetic liability across 1,380 medical conditions in females and males recorded in the Vanderbilt University Medical Center electronic health record (EHR) database. After adjusting for age and genetic ancestry, we found that European descent males with higher PCOSPRS were significantly more likely to develop cardiovascular diseases than females at the same level of genetic risk, while females had a higher odds of developing T2D. Based on observed significant associations, we tested the relationship between PRS for comorbid conditions (e.g., T2D, body mass index, hypertension, etc.) and found that only PRS generated for BMI and T2D were associated with a PCOS diagnosis. We then further decomposed the T2DPRS association with PCOS by adjusting the model for measured BMI and BMIresidual (enriched for the environmental contribution to BMI). Results demonstrated that genetically regulated BMI primarily accounted for the relationship between T2DPRS and PCOS. This was further supported in a mediation analysis, which only revealed clinical BMI measurements, but not BMIresidual, as a strong mediator for both sexes. Overall, our findings show that the genetic architecture of PCOS has distinct metabolic sex differences, but these associations are only apparent when PCOSPRS is explicitly modeled. It is possible that these pathways are less explained by the direct genetic risk of metabolic traits than they are by the risk factors shared between them, which can be influenced by biological variables such as sex.

scholarly journals Genetic Sex Effects of Polycystic Ovary Syndrome Reveal Distinct Metabolic Etiology

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A766-A766
Author(s):  
Ky’Era Actkins ◽  
Digna R Velez Edwards ◽  
Melinda Aldrich ◽  
Lea K Davis
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Genetic Risk ◽  
Polycystic Ovary ◽  
Medical Center ◽  
Genetic Relationships ◽  
African Descent ◽  
Polygenic Risk Score ◽  
Polycystic Ovaries ◽  
Ovary Syndrome ◽  
Increased Risk

Abstract Females with polycystic ovary syndrome (PCOS) have an increased risk of developing metabolic disorders such as insulin resistance, obesity, and type 2 diabetes (T2D). High-risk groups or individuals with a family history are more likely to have a greater genetic susceptibility to these diseases, which drastically increases their risk of developing other chronic health conditions. In this study, we systematically evaluated the bidirectional genetic burden of PCOS and its comorbidities among females and males. First, we analyzed the pleiotropic effects of the PCOS polygenic risk score (PRS), a measurement of genetic liability to PCOS, across 1,857 medical conditions recorded in the Vanderbilt University Medical Center electronic health record. We conducted a phenome-wide association study (PheWAS) adjusted for median age, sex, and genetic ancestry. In the European sex-combined model (n = 72,824), we observed that PCOS PRS was significantly (Bonferroni corrected p < 7.86e-06) associated with T2D (OR = 1.11, p = 8.75e-08) and hypertension (OR = 1.06, p = 1.13e-07) in addition to polycystic ovaries (OR = 1.11, p = 1.91e-07). In the sex-stratified model, we found that males (n = 32,022) with a higher PRS for PCOS were more likely to develop cardiovascular diseases (CVD) compared to females (n = 40,802) who had higher odds of developing T2D. Although we were underpowered to detect any phenome-wide significant effects in our African descent sample (n=15,283), uterine leiomyoma (OR = 1.24, p = 3.79e-03), osteoarthritis (OR = 1.21, p = 3.94e-03), and benign neoplasm of uterus (OR = 1.24, p = 4.00e-03) were the top three nominal significant results (p < 0.05) in females (n = 9,418). To understand the genetic relationships observed in the PheWAS, we used LD score regression to determine the genetic correlation between the phenotypes. We found that PCOS was positively correlated with T2D (rg = 31%), systolic blood pressure (rg = 12%), and pulse pressure (rg = 15%). However, we found no significant associations between the genetic risk of CVD and PCOS diagnosis in the European or African descent samples. Our findings show that the genetic architecture of PCOS has distinct metabolic sex differences, but the genetic risk of those comorbidities is not predictive of a PCOS diagnosis. This suggests that other drivers are contributing to the endocrine and cardiovascular comorbid signatures that underlie PCOS.

scholarly journals Evidence From Men for Ovary-independent Effects of Genetic Risk Factors for Polycystic Ovary Syndrome

2021 ◽  
Author(s):  
Jia Zhu ◽  
Natàlia Pujol-Gualdo ◽  
Laura B L Wittemans ◽  
Cecilia M Lindgren ◽  
Triin Laisk ◽  
...  
Keyword(s):  
Risk Factors ◽  
Polycystic Ovary Syndrome ◽  
Genetic Risk ◽  
Ovarian Function ◽  
Polycystic Ovary ◽  
Density Lipoprotein ◽  
Genetic Risk Factors ◽  
Risk Scores ◽  
Androgenic Alopecia ◽  
Ovary Syndrome

Abstract Context Polycystic ovary syndrome (PCOS) is characterized by ovulatory dysfunction and hyperandrogenism and can be associated with cardiometabolic dysfunction, but it remains unclear which of these features are inciting causes and which are secondary consequences. Objective To determine whether ovarian function is necessary for genetic risk factors for PCOS to produce nonreproductive phenotypes. Design, Setting, and Participants Cohort of 176 360 men in the UK Biobank and replication cohort of 37 348 men in the Estonian Biobank. Main Outcome Measures We calculated individual PCOS polygenic risk scores (PRS), tested for association of these PRS with PCOS-related phenotypes using linear and logistic regression and performed mediation analysis. Results For every 1 SD increase in the PCOS PRS, men had increased odds of obesity (odds ratio [OR]: 1.09; 95% CI, 1.08-1.10; P = 1 × 10-49), type 2 diabetes mellitus (T2DM) (OR: 1.08; 95% CI, 1.05-1.10; P = 3 × 10-12), coronary artery disease (CAD) (OR: 1.03; 95% CI, 1.01-1.04; P = 0.0029), and marked androgenic alopecia (OR: 1.03; 95% CI, 1.02-1.05; P = 3 × 10-5). Body mass index (BMI), hemoglobin A1c, triglycerides, and free androgen index increased as the PRS increased, whereas high-density lipoprotein cholesterol and SHBG decreased (all P < .0001). The association between the PRS and CAD appeared to be completely mediated by BMI, whereas the associations with T2DM and marked androgenic alopecia appeared to be partially mediated by BMI. Conclusions Genetic risk factors for PCOS have phenotypic consequences in men, indicating that they can act independently of ovarian function. Thus, PCOS in women may not always be a primary disorder of the ovaries.

scholarly journals Metabolic syndrome and polycystic ovary syndrome... and vice versa

2009 ◽  
Vol 53 (2) ◽  
pp. 227-237 ◽  
Author(s):  
Eleni Kandaraki ◽  
Charikleia Christakou ◽  
Evanthia Diamanti-Kandarakis
Keyword(s):  
Metabolic Syndrome ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Adult Women ◽  
Ovary Syndrome ◽  
Clinical Observations ◽  
The Metabolic Syndrome ◽  
Increased Risk ◽  
The Relationship ◽  
Endocrine Features

The metabolic syndrome (MS) and the polycystic ovary syndrome (PCOS) appear to be interrelated, although they are distinct entities. Women with PCOS appear to be commonly affected by MS, while women with MS may display reproductive or endocrine features of PCOS. These clinical observations appear to be only partly attributable to the association of both syndromes with obesity and imply a reciprocal pathophysiologic relationship between PCOS and MS with potentially significant clinical sequelae. Adult women with MS are at a greater risk of developing cardiovascular disease; women with PCOS also appear to carry such an increased risk in their postmenopausal life. Conversely, women with MS may experience reproductive disturbances, reminiscent of PCOS, more commonly than their counterparts from the general population. This review presented the current epidemiology of MS in adults and adolescents with PCOS, as well as the limited amount of data on the prevalence of features of PCOS among women with MS or MS features. We also discuss the potential pathophysiologic mechanisms underlying the relationship between these interweaving, but distinct, syndromes.

scholarly journals Polycystic ovary syndrome and increased risk of psychiatric disorders

2020 ◽  
Vol 8 (6) ◽  
pp. 133-137
Author(s):  
Mohadetheh Moulana PhD ◽  
Anju P Sukumaran MD
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Medical Center ◽  
Psychological Disorders ◽  
Well Being ◽  
Reproductive Age ◽  
Physical And Mental Health ◽  
Ovary Syndrome ◽  
Increased Risk ◽  
First Time

Aim: This study is aimed to assess, for the first time the prevalence of polycystic ovary syndrome (PCOS) and associated psychological disorders among women at reproductive age in Mississippi. Methods: The data was collected through “the Patient Cohort Explorer” system at the University of Mississippi Medical Center (UMMC) from January 2013 to December 2018. De-identified patients were searched with diagnosis code for PCOS, age, ethnicity, and associated diagnosis including weight gain, anxiety, depression, attention-deficit/hyperactivity disorder (ADHD), and other psychological concerns. Results: Collected data from 166,748 females (19-45 years) showed 1.4% (95% CI: 1.32 – 1.44) prevalence of PCOS in women seen in UMMC clinics during the period of study. Almost 51% of patients with PCOS suffered from one or more psychological disorders; anxiety 21% (95% CI: 19.3 – 22.6), depression 20% (95% CI: 18.9 – 22.1), ADHD 3.2% (95% CI: 2.6 – 4.0), and bipolar disorder 2.5% (95% CI: 1.9 – 3.2). In addition, prevalence values suggest a positive correlation between obesity, anxiety, and depression in PCOS patients. Conclusion: Results from this study provide 1) for the first time an estimate regarding the prevalence of PCOS and associated psychological disorders in women with PCOS in a Mississippi, 2) associated psychological disorders in PCOS women may be diverse based on race and ethnicity. Our data clearly highlight that the psychological well-being of women with PCOS are affected. Therefore, it is critical for the primary care and specialty clinics to use appropriate psychological screenings. Left undiagnosed and/or untreated, chronic psychological disorders may exacerbate physical and mental health conditions.

scholarly journals The Relationship between Clinico-Biochemical Characteristics and Psychiatric Distress in Young Women with Polycystic Ovary Syndrome

2008 ◽  
Vol 36 (6) ◽  
pp. 1188-1196 ◽  
Author(s):  
E Adali ◽  
R Yildizhan ◽  
M Kurdoglu ◽  
A Kolusari ◽  
T Edirne ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Polycystic Ovary Syndrome ◽  
Emotional Distress ◽  
Polycystic Ovary ◽  
Resistance Index ◽  
Control Group ◽  
Ovary Syndrome ◽  
Biochemical Characteristics ◽  
Increased Risk ◽  
The Relationship

The relationship between clinico-biochemical characteristics and self-reported psychological parameters in 42 women with polycystic ovary syndrome (PCOS) and 42 age-matched healthy controls was examined. The General Health Questionnaire was used (GHQ-12) to ascertain emotional distress and the Beck Depression Inventory (BDI) to determine depressive symptoms. Emotional distress, depressive symptoms, hirsutism score, body mass index (BMI), waist-to-hip ratio (WHR), luteinizing hormone/follicle-stimulating hormone ratio, serum total testosterone, dehydroepiandrosterone sulphate levels and the insulin resistance index were significantly greater in women with PCOS than in healthy women. The BDI and GHQ-12 scores of the women with PCOS were significantly higher than those of the control group (BDI, 11.69 ± 9.49 vs 5.80 ± 4.58; GHQ-12, 3.38 ± 3.38 vs 1.54 ± 1.97, respectively), and BMI and WHR were positively correlated with the BDI and GHQ-12 scores. Clinicians should be aware of the increased risk of emotional distress and depression in women with PCOS, especially those who are obese, and of the need to screen these patients for such symptoms.

scholarly journals A genetic risk score is associated with polycystic ovary syndrome-related traits

2015 ◽  
Vol 31 (1) ◽  
pp. 209-215 ◽  
Author(s):  
Hyejin Lee ◽  
Jee-Young Oh ◽  
Yeon-Ah Sung ◽  
Hye Won Chung
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Risk Score ◽  
Genetic Risk ◽  
Polycystic Ovary ◽  
Genetic Risk Score ◽  
Ovary Syndrome

scholarly journals Urinary bisphenol A in women with polycystic ovary syndrome – a possible suppressive effect on steroidogenesis?

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Zora Lazúrová ◽  
Jana Figurová ◽  
Beáta Hubková ◽  
Jana Mašlanková ◽  
Ivica Lazúrová
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Bisphenol A ◽  
Steroid Hormones ◽  
Polycystic Ovary ◽  
Suppressive Effect ◽  
Human Reproduction ◽  
Control Group ◽  
Ovary Syndrome ◽  
Ovarian Steroidogenesis ◽  
The Relationship

Abstract Objectives There is a growing evidence indicating an impact of endocrine distrupting chemicals such as bisphenol A (BPA) on human reproduction. Its higher levels in serum or urine have been documented in women with polycystic ovary syndrome (PCOS), however the relationship to ovarian steroidogenesis remains unclear. Aim of the study was to compare urinary BPA (U-BPA) concentrations among PCOS women and control group. Second aim was to assess the relationship of U-BPA to ovarian steroidogenesis in the group with PCOS. Methods Eighty six Caucasian women (age 28.5 ± 5.1 years) diagnosed with PCOS and 32 controls of age 24.9 ± 4.4 years were included in the study. Fasting blood samples were analyzed for biochemical parameters and steroid hormones. U-BPA was measured in the morning urine sample using high pressure liquid chromatography. Results PCOS women had significantly higher U-BPA as compared with control group (p=0.0001). Those with high levels of U-BPA (U-BPA ≥2.14 ug/g creatinine) demonstrated higher serum insulin (p=0.029) and HOMA IR (p=0.037), lower serum estrone (p=0.05), estradiol (p=0.0126), FSH (p=0.0056), and FAI (p=0.0088), as compared with low-BPA group (U- BPA <2.14 ug/g creatinine). In PCOS women, U-BPA positively correlated with age (p=0.0026; R2=0.17), negatively with estradiol (p=0.0001, R2=0.5), testosterone (p=0.0078, R2=0.15), free-testosterone (p=0.0094, R2=0.12) and FAI (p=0.0003, R2=0.32), respectively. Conclusions PCOS women have significantly higher U-BPA concentrations than healthy controls. U-BPA positively correlates with age and negatively with ovarian steroid hormones suggesting a possible suppressive effect of bisphenol A on ovarian steroidogenesis.

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