REPLICATION STUDY REVEALS ASSOCIATION OF SELECTED GWAS GLOBAL VARIANTS WITH PCOS IN INDIAN WOMEN

Abstract

Polycystic ovary syndrome (PCOS) is a complex metabolic and endocrine disorder affecting reproductive-age women. Diagnosis is challenging in adolescents due to characteristic symptoms after menarche. Hence, it is important to identify early markers for an accurate diagnosis of PCOS in teenage girls. This study identifies eight variants from four GWAS genes associated with PCOS in the Indian population. About 250 PCOS and 300 control Indian women aged 18-34 were recruited, and their blood samples, written informed consent, and sociodemographic data were obtained. Genomic DNA was isolated from peripheral vein blood and genotyped for variants from FSHR, LHCGR, and THADA genes by ARMS PCR and DENND1A by PCR-RFLP. Odds ratios (OR) were calculated to ascertain the association of selected variants with PCOS, with confidence intervals maintained at 95%. Of the eight intronic GWAS variants, five variants, rs11692782, rs2349415 from FSHR, rs10818854 from DENND1A, rs12478601, rs13429458 from THADA genes were found to be associated with PCOS women in India. In-silico study showed rs13429458 of THADA being CADD-tolerated and others are non-pathogenic. This study identifies five SNPs associated with PCOS in Indian women, which were previously reported to show association in other ethnic populations, and thus may be useful in early diagnosis of PCOS.