BACKGROUND PCOS is a common endocrine disorder that is characterized by hyperandrogenism and chronic anovulation and is the leading cause of female infertility. It is a heterogeneous disorder with the involvement of multiple gene and environmental interactions. This study identified variants that are known to confer susceptibility identified by Genome wide association studies (GWAS) in other ethnicities and replicated the same in individuals with PCOS of Indian ethnicity. METHODS Study subjects (n=600) were recruited. Blood samples, demographic and clinical details were collected after obtaining informed consent. Fifteen variants were selected from GWA studies from other ethnicities and genotyped in half of the recruited samples (n=300) using MassARRAYiPLEX™. Replication of significant variants generated from preliminary data was carried out by PCR and direct sequencing in remainder of the samples (n=300). Insilco analysis for significant variants was performed using software namely CADD, GWAVA, FATHMM-MKL. Relevant statistics were used to ascertain significance. RESULTS The mean age of patients and controls was 24.26±3.22 and 30.19±11.21 years respectively. Of the 15 variants, 3 variants (rs13405728 in LHCGR; rs13429458 in THADA and rs2209972 IDE genes) were found to be associated with PCOS. The association was successfully replicated in an independent cohort. Insilico analysis categorized two variants (rs13429458-THADA and rs2209972-IDE genes) as deleterious. CONCLUSION We demonstrate the association of variants in genes namely LHCGR, THADA and IDE with an increased risk of PCOS. Genotyping for these variants aids in identifying at-risk individuals which is crucial as appropriate early interventions may benefit the patient.

中文翻译：

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汇总的遗传分析确定了在印度族裔中对PCOS敏感性增强的变体。

背景技术PCOS是一种常见的内分泌失调，其特征是雄激素过多症和慢性无排卵，是女性不孕症的主要原因。它是一种涉及多种基因和环境相互作用的异质性疾病。这项研究确定了已知可赋予其他族裔通过基因组广泛关联研究（GWAS）鉴定出的易感性的变体，并在具有印度裔PCOS的个体中复制了这些变体。方法招募研究对象（n = 600）。在获得知情同意后，收集血液样本，人口统计学和临床​​细节。从其他种族的GWA研究中选择了15个变体，并使用MassARRAYiPLEX™在一半的招募样本（n = 300）中进行了基因分型。通过PCR和直接测序在其余样品中复制从初步数据生成的重要变体（n = 300）。使用软件CADD，GWAVA，FATHMM-MKL对重要变体进行Insilco分析。相关统计数据用于确定重要性。结果患者和对照组的平均年龄分别为24.26±3.22岁和30.19±11.21岁。在15个变体中，发现3个变体（LHCGR中的rs13405728； THADA中的rs13429458和rs2209972 IDE基因）与PCOS相关。该关联已成功复制到一个独立的队列中。Insilico分析将两个变体（rs13429458-THADA和rs2209972-IDE基因）分类为有害。结论我们证明了LHCGR，THADA和IDE基因变异与PCOS风险增加有关。