{"doi":"10.3389/fendo.2020.00274","title":"PCOS-GWAS Susceptibility Variants in THADA, INSR, TOX3, and DENND1A Are Associated With Metabolic Syndrome or Insulin Resistance in Women With PCOS","abstract":"Polycystic ovary syndrome is characterized by reproductive and metabolic disturbances throughout the female lifespan. Therefore, this study aimed to determine whether genome-wide association studies (GWAS)-identified risk variants for PCOS could confer risk of metabolic syndrome (MS) or insulin resistance (IR). Fifteen independent SNPs mapping to 11 GWAS loci genotyped in a total of 2082 Han Chinese women independent of previous GWAS and phenotype-genotype correlations were assessed. The CC group for rs12478601 in THADA was associated with decreased rate of MS after adjustment for age (23.2% vs 27%, P = 0.042, OR = 0.81). Using a dominant model, the GG+AG group for rs2059807 in INSR was associated with increased risk of MS after adjustment for age (26.8% vs 22.5%, P = 0.023, OR = 1.27). The GG + GT group for rs4784165 in TOX3 was found to be associated with an increased rate of IR after adjustment for age and BMI(53.3% vs 48.5%, P = 0.027, OR = 1.27).The GG+AG group for rs2479106 in DENND1A was associated with a decreased rate of IR (48.3% vs 53.6%, adjusted P = 0.039, OR = 0.80). After exclusion of PCOS cases with a family history of diabetes, hypertension, or dyslipidemia, the phenotype-genotype correlations between the genes INSR and TOX3 and MS or IR were still significant (P < 0.05). Three SNPs (rs13429458 in THADA, rs10818854 in DENND1A, and rs2059807 in INSR) were significantly associated with IR; however, their association was not significant after adjustment for age and BMI. This genotype-phenotype study thus provides clues that THADA, INSR, TOX3, and DENND1A play a role in PCOS possibly through a metabolic disorder-related pathway.","journal":"Frontiers in Endocrinology","year":2020,"id":58635,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":71,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9562,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":307602,"name":"Jingyu Li","orcid":"0000-0003-0136-532X","position":1,"is_corresponding":false},{"id":309721,"name":"Shizhen Su","orcid":null,"position":2,"is_corresponding":false},{"id":307603,"name":"Yongzhi Cao","orcid":"0000-0001-9517-7332","position":3,"is_corresponding":false},{"id":130567,"name":"Zhao Wang","orcid":"0000-0003-0418-6845","position":4,"is_corresponding":false},{"id":307604,"name":"Shigang Zhao","orcid":"0000-0002-7407-9220","position":5,"is_corresponding":false},{"id":307605,"name":"Han Zhao","orcid":"0000-0001-9515-7534","position":6,"is_corresponding":false},{"id":307601,"name":"Ye Tian","orcid":"0000-0003-2972-8516","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-18T21:07:33.416320Z","pmid":"32425888","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}