Pathway Analysis Based on a Genome-Wide Association Study of Polycystic Ovary Syndrome

Abstract

BackgroundPolycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age, and it is affected by both environmental and genetic factors. Although the genetic component of PCOS is evident, studies aiming to identify susceptibility genes have shown controversial results. This study conducted a pathway-based analysis using a dataset obtained through a genome-wide association study (GWAS) to elucidate the biological pathways that contribute to PCOS susceptibility and the associated genes.MethodsWe used GWAS data on 636,797 autosomal single nucleotide polymorphisms (SNPs) from 1,221 individuals (432 PCOS patients and 789 controls) for analysis. A pathway analysis was conducted using meta-analysis gene-set enrichment of variant associations (MAGENTA). Top-ranking pathways or gene sets associated with PCOS were identified, and significant genes within the pathways were analyzed.ResultsThe pathway analysis of the GWAS dataset identified significant pathways related to oocyte meiosis and the regulation of insulin secretion by acetylcholine and free fatty acids (all nominal gene-set enrichment analysis (GSEA) P-values < 0.05). In addition, INS, GNAQ, STXBP1, PLCB3, PLCB2, SMC3 and PLCZ1 were significant genes observed within the biological pathways (all gene P-values < 0.05).ConclusionsBy applying MAGENTA pathway analysis to PCOS GWAS data, we identified significant pathways and candidate genes involved in PCOS. Our findings may provide new leads for understanding the mechanisms underlying the development of PCOS.

The key long non‐coding RNA screening and validation between germinal vesicle and metaphase II of porcine oocyte in vitro maturation

“…The RNA-seq results also found that SFRP4, PGR, PGRMC1, PLCZ1, ZMIZ1 involved in the oocyte nuclear transcription process, hormone secretion, cumulus cell expansion and oocyte meiosis process-related gene expression (Luciano, Lodde, Franciosi, Ceciliani, & Peluso, 2010;Nagyova, Scsukova, Kalous, & Mlynarcikova, 2014;Shim et al, 2015;Yoon et al, 2012).…”

“…The RNA‐seq results also found that SFRP4 , PGR , PGRMC1 , PLCZ1 , ZMIZ1 involved in the oocyte nuclear transcription process, hormone secretion, cumulus cell expansion and oocyte meiosis process‐related gene expression (Luciano, Lodde, Franciosi, Ceciliani, & Peluso, ; Nagyova, Scsukova, Kalous, & Mlynarcikova, ; Shim et al, ; Yoon et al, ). Meanwhile, we found that ZSCAN4111 was an essential gene of RNA transcriptase II, regulating the development of primitive follicles in the process of oocyte maturation (Teng et al, ).…”

Single-cell analysis of differences in transcriptomic profiles of oocytes and cumulus cells at GV, MI, MII stages from PCOS patients

“…The absence of these transcription factors can arrest oocyte maturation2526. PLCZ1 , which is significantly related to oocyte meiosis and the regulation of insulin secretion, can induce the activation of oocytes at the MII stage so that sperm and oocytes can fuse well2728. The expression of SFRP4 and ZMIZ1 , which are regulators of ovulation and luteinization, is lower in PCOS oocytes, indicating that the abnormal microenvironment of PCOS impacts luteinization negatively2930.…”

Computational Systems Analysis on Polycystic Ovarian Syndrome (PCOS)

“…Shen et al [130] also found several enriched pathways such as cancer pathways and MAPK signaling and ontologies including regulation of metabolic process from both constructed networks that might be responsible in both PCOS and IR [130]. Shim association study (GWAS) dataset of PCOS and successfully identified several PCOS pathways associated with ovulation and insulin secretion [131]. Kori et al [132] used PPI and pathway analysis by integrating three microarray datasets of PCOS with PPI data, performing the pathway enrichment analysis and comparing the PCOS results with ovarian cancer and endometriosis.…”