title: The role of epistasis in the etiology of Polycystic Ovary Syndrome among Indian women: SNP-SNP and SNP-environment interactions.
abstract: Polycystic Ovary Syndrome (PCOS) is the most common endocrinopathy in women of reproductive age. It is a heterogeneous androgen excess disorder determined by the interaction of multiple genetic and environmental factors. Our earlier analysis on a panel of six candidate genes (Androgen receptor CAG repeats, Follistatin, Luteinizing hormone β subunit, Calpain10, Insulin receptor substrate-1 and PPARγ) based on 250 PCOS cases and 299 controls revealed significant association patterns with PCOS among South-Indian women. We report here for the first time, the SNP-SNP and SNP-environment interactions of these genes in the same cohort. Both multivariate logistic regression as well as epistasis analysis (using Multifactor dimensionality reduction software) yielded significant results (P < 0.05). All CAPN10 SNPs show association (either risk-conferring or protective) in the obese group, highlighting the importance of this gene in the PCOS pathophysiology. LHP7(LHβ) and UCSNP44(CAPN10) emerged to be the prominent SNPs in the SNP-SNP interaction analysis. The best SNP-SNP interaction model was obtained between CAPN10 UCSNP-44 and PPARγ His447His, implying a significant metabolic component in the PCOS pathology. Replicating our findings in BMI-specific cohorts in different ethnic populations would be warranted in future to identify the physiological networks in PCOS.
authors.affiliation: Molecular Anthropology Group, Biological Anthropology Unit, Indian Statistical Institute, Hyderabad, Andhra Pradesh, India.
authors.forename: Shilpi
authors.initials: S
authors.lastname: Dasgupta
authors.forename: B Mohan
authors.initials: BM
authors.lastname: Reddy
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D002874:Chromosome Mapping; D004843:Epistasis, Genetic; D005260:Female; D005787:Gene Frequency; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006728:Hormones / Q000097:blood; D006801:Humans; D007194:India; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D055815:Young Adult
chemical_list: D006728:Hormones
keywords: India; PCOS; SNP‐SNP interaction; SNP‐environment interaction; epistasis