scholarly journals Polycystic Ovary Syndrome and Risk of Five Common Psychiatric Disorders Among European Women: A Two-Sample Mendelian Randomization Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Luyang Jin ◽  
Jia'en Yu ◽  
Yuxiao Chen ◽  
Haiyan Pang ◽  
Jianzhong Sheng ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Genetic Variants ◽  
Mendelian Randomization ◽  
Polycystic Ovary ◽  
Causal Effects ◽  
Ovary Syndrome ◽  
Inverse Variance ◽  
Simulation Extrapolation ◽  
Weighted Median ◽  
European Populations

Background: Observational studies have implied an association between polycystic ovary syndrome (PCOS) and psychiatric disorders. Here we examined whether PCOS might contribute causally to such disorders, focusing on anxiety disorder (AD), bipolar disorder (BIP), major depression disorder (MDD), obsessive compulsive disorder (OCD), and schizophrenia (SCZ).Methods: Causality was explored using two-sample Mendelian randomization (MR) with genetic variants as instrumental variables. The genetic variants were from summary data of genome-wide association studies in European populations. First, potential causal effects of PCOS on each psychiatric disorder were evaluated, and then potential reverse causality was also assessed once PCOS was found to be causally associated with any psychiatric disorder. Causal effects were explored using inverse variance weighting, MR-Egger analysis, simulation extrapolation, and weighted median analysis.Results: Genetically predicted PCOS was positively associated with OCD based on inverse variance weighting (OR 1.339, 95% CI 1.083–1.657, p = 0.007), simulation extrapolation (OR 1.382, 95% CI 1.149–1.662, p = 0.009) and weighted median analysis (OR 1.493, 95% CI 1.145–1.946, p = 0.003). However, genetically predicted OCD was not associated with PCOS. Genetically predicted PCOS did not exert causal effects on AD, BIP, MDD, or SCZ.Conclusions: In European populations, PCOS may be a causal factor in OCD, but not AD, BIP, MDD, or SCZ.

Circulating adiponectin levels and systemic lupus erythematosus: a two-sample Mendelian randomization study

Rheumatology ◽  
2020 ◽  
Author(s):  
Yi-Lin Dan ◽  
Peng Wang ◽  
Zhongle Cheng ◽  
Qian Wu ◽  
Xue-Rong Wang ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Instrumental Variables ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Causal Effects ◽  
European Ancestry ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Inverse Variance ◽  
Weighted Median

Abstract Objectives Several studies have reported increased serum/plasma adiponectin levels in SLE patients. This study was performed to estimate the causal effects of circulating adiponectin levels on SLE. Methods We selected nine independent single-nucleotide polymorphisms that were associated with circulating adiponectin levels (P < 5 × 10−8) as instrumental variables from a published genome-wide association study (GWAS) meta-analysis. The corresponding effects between instrumental variables and outcome (SLE) were obtained from an SLE GWAS analysis, including 7219 cases with 15 991 controls of European ancestry. Two-sample Mendelian randomization (MR) analyses with inverse-variance weighted, MR-Egger regression, weighted median and weight mode methods were used to evaluate the causal effects. Results The results of inverse-variance weighted methods showed no significantly causal associations of genetically predicted circulating adiponectin levels and the risk for SLE, with an odds ratio (OR) of 1.38 (95% CI 0.91, 1.35; P = 0.130). MR-Egger [OR 1.62 (95% CI 0.85, 1.54), P = 0.195], weighted median [OR 1.37 (95% CI 0.82, 1.35), P = 0.235) and weighted mode methods [OR 1.39 (95% CI 0.86, 1.38), P = 0.219] also supported no significant associations of circulating adiponectin levels and the risk for SLE. Furthermore, MR analyses in using SLE-associated single-nucleotide polymorphisms as an instrumental variable showed no associations of genetically predicted risk of SLE with circulating adiponectin levels. Conclusion Our study did not find evidence for a causal relationship between circulating adiponectin levels and the risk of SLE or of a causal effect of SLE on circulating adiponectin levels.

scholarly journals Mendelian randomization analysis identified potential genes pleiotropically associated with polycystic ovary syndrome

2021 ◽  
Author(s):  
Qian Sun ◽  
Yuan Gao ◽  
Jingyun Yang ◽  
Jiayi Lu ◽  
Wen Feng ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Whole Blood ◽  
Multiple Testing ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Polycystic Ovary ◽  
Research Question ◽  
Ovary Syndrome ◽  
Unclear Etiology ◽  
Eqtl Data

Research question: Polycystic ovary syndrome (PCOS) is a common endocrine disorder with unclear etiology. Are there any genes that are pleiotropically or potentially causally associated with PCOS? Design: We applied the summary data-based Mendelian randomization (SMR) method integrating genome-wide association study (GWAS) for PCOS and expression quantitative trait loci (eQTL) data to identify genes that were pleiotropically associated with PCOS. We performed separate SMR analysis using eQTL data in the ovary and whole blood. Results: Although no genes showed significant pleiotropic association with PCOS after correction for multiple testing, some of the genes exhibited suggestive significance. RPS26 showed the strongest suggestive pleiotropic association with PCOS in both SMR analyses (β[SE]=0.10[0.03], PSMR=1.72*10-4 for ovary; β[SE]=0.11[0.03], PSMR=1.40*10-4 for whole blood). PM20D1 showed the second strongest suggestive pleiotropic association with PCOS in the SMR analysis using eQTL data for the whole blood, and was also among the top ten hit genes in the SMR analysis using eQTL data for the ovary. Two other genes, including CTC-457L16.2 and NEIL2, were among the top ten hit genes in both SMR analyses. Conclusion: We identified multiple genes that were potentially involved in the pathogenesis of PCOS. Our findings provided helpful leads to a better understanding of the mechanisms underlying PCOS, and revealed potential therapeutic targets for the effective treatment of PCOS.

scholarly journals The role of polymorphism in various potential genes on polycystic ovary syndrome susceptibility and pathogenesis

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Hiral Chaudhary ◽  
Jalpa Patel ◽  
Nayan K. Jain ◽  
Rushikesh Joshi
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Genetic Variants ◽  
Polycystic Ovary ◽  
Association Studies ◽  
Reproductive Age ◽  
Biosynthesis Pathway ◽  
Cytochrome P450 Enzymes ◽  
Adrenal Androgen ◽  
Ovary Syndrome ◽  
Altered Expression

AbstractPolycystic ovary syndrome (PCOS) is the most common endocrinopathies affecting the early reproductive age in women, whose pathophysiology perplexes many researchers till today. This syndrome is classically categorized by hyperandrogenism and/or hyperandrogenemia, menstrual and ovulatory dysfunction, bulky multi follicular ovaries on Ultrasonography (USG), and metabolic abnormalities such as hyperinsulinemia, dyslipidemia, obesity. The etiopathogenesis of PCOS is not fully elucidated, but it seems that the hypothalamus-pituitary-ovarian axis, ovarian, and/or adrenal androgen secretion may contribute to developing the syndrome. Infertility and poor reproductive health in women’s lives are highly associated with elevated levels of androgens. Studies with ovarian theca cells taken from PCOS women have demonstrated increased androgen production due to augmented ovarian steroidogenesis attributed to mainly altered expression of critical enzymes (Cytochrome P450 enzymes: CYP17, CYP21, CYP19, CYP11A) in the steroid hormone biosynthesis pathway. Despite the heterogeneity of PCOS, candidate gene studies are the widely used technique to delineate the genetic variants and analyze for the correlation of androgen biosynthesis pathway and those affecting the secretion or action of insulin with PCOS etiology. Linkage and association studies have predicted the relationship between genetic variants and PCOS risk among families or populations. Several genes have been proposed as playing a role in the etiopathogenesis of PCOS, and the presence of mutations and/or polymorphisms has been discovered, which suggests that PCOS has a vital heritable component. The following review summarizes the influence of polymorphisms in crucial genes of the steroidogenesis pathway leading to intraovarian hyperandrogenism which can result in PCOS.

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