{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T21:02:16Z","timestamp":1789506136946,"version":"build-2803163510"},"reference-count":84,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T00:00:00Z","timestamp":1661731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>Genome-wide association studies (GWAS) have identified several common variants associated with polycystic ovary syndrome (PCOS). However, the etiology behind PCOS remains incomplete. Available evidence suggests a potential genetic correlation between PCOS and type 2 diabetes (T2D). The publicly available data may provide an opportunity to enhance the understanding of the PCOS etiology. Here, we quantified the polygenic overlap between PCOS and T2D using summary statistics of PCOS and T2D and then identified the novel genetic variants associated with PCOS behind this phenotypic association. A bivariate causal mixture model (MiXeR model) found a moderate genetic overlap between PCOS and T2D (Dice coefficient = 44.1% and after adjusting for body mass index, 32.1%). The conditional\/conjunctional false discovery rate method identified 11 potential risk variants of PCOS conditional on associations with T2D, 9 of which were novel and 6 of which were jointly associated with two phenotypes. The functional annotation of these genetic variants supports a significant role for genes involved in lipid metabolism, immune response, and the insulin signaling pathway. An expression quantitative trait locus functionality analysis successfully repeated that 5 loci were significantly associated with the expression of candidate genes in many tissues, including the whole blood, subcutaneous adipose, adrenal gland, and cerebellum. We found that <jats:italic>SCN2A<\/jats:italic> gene is co-localized with PCOS in subcutaneous adipose using GWAS-eQTL co-localization analyses. A total of 11 candidate genes were differentially expressed in multiple tissues of the PCOS samples. These findings provide a new understanding of the shared genetic architecture between PCOS and T2D and the underlying molecular genetic mechanism of PCOS.<\/jats:p>","DOI":"10.3389\/fgene.2022.905716","type":"journal-article","created":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T05:06:05Z","timestamp":1661749565000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Identifying novel genetic loci associated with polycystic ovary syndrome based on its shared genetic architecture with type 2 diabetes"],"prefix":"10.3389","volume":"13","author":[{"given":"Xiaoyi","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujia","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zechen","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dafang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,8,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1318","DOI":"10.1126\/science.aaz1776","article-title":"The GTEx Consortium atlas of genetic regulatory effects across human tissues","volume":"369","author":"Aguet","year":"2020","journal-title":"Science"},{"key":"B2","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1186\/s12864-018-4573-5","article-title":"Identification of a novel Dlg2 isoform differentially expressed in IFN\u03b2-producing plasmacytoid dendritic cells","volume":"19","author":"Ali","year":"2018","journal-title":"BMC Genomics"},{"key":"B3","doi-asserted-by":"publisher","first-page":"e1003455","DOI":"10.1371\/journal.pgen.1003455","article-title":"Improved detection of common variants associated with schizophrenia and bipolar disorder using pleiotropy-informed conditional false discovery rate","volume":"9","author":"Andreassen","year":"2013","journal-title":"PLoS Genet."},{"key":"B4","doi-asserted-by":"publisher","first-page":"2555","DOI":"10.1093\/hmg\/ddp187","article-title":"Characterization of six human disease-associated inversion polymorphisms","volume":"18","author":"Antonacci","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"B5","doi-asserted-by":"publisher","first-page":"16057","DOI":"10.1038\/nrdp.2016.57","article-title":"Polycystic ovary syndrome","volume":"2","author":"Azziz","year":"2016","journal-title":"Nat. Rev. Dis. Prim."},{"key":"B6","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1080\/13813455.2018.1499120","article-title":"Insulin resistance and oxidative marker in women with PCOS","volume":"126","author":"Bannigida","year":"2020","journal-title":"Arch. Physiol. Biochem."},{"key":"B7","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.tem.2004.02.006","article-title":"Disregulated glyceroneogenesis: PCK1 as a candidate diabetes and obesity gene","volume":"15","author":"Beale","year":"2004","journal-title":"Trends Endocrinol. Metab."},{"key":"B8","doi-asserted-by":"publisher","first-page":"e8269","DOI":"10.1371\/journal.pone.0008269","article-title":"Nucleotide, cytogenetic and expression impact of the human chromosome 8p23.1 inversion polymorphism","volume":"4","author":"Bosch","year":"2009","journal-title":"PloS one"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1790","DOI":"10.1101\/gr.137323.112","article-title":"Annotation of functional variation in personal genomes using RegulomeDB","volume":"22","author":"Boyle","year":"2012","journal-title":"Genome Res."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.1038\/ng.3406","article-title":"An atlas of genetic correlations across human diseases and traits","volume":"47","author":"Bulik-Sullivan","year":"2015","journal-title":"Nat. Genet."},{"key":"B35","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/s41586-018-0579-z","article-title":"The UK Biobank resource with deep phenotyping and genomic data","volume":"562","author":"Bycroft","year":"2018","journal-title":"Nature"},{"key":"B11","doi-asserted-by":"publisher","first-page":"11827","DOI":"10.3390\/ijms222111827","article-title":"Cathepsin B regulates mice granulosa cells' apoptosis and proliferation in vitro","volume":"22","author":"Chen","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B12","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1046\/j.1365-2265.2000.00884.x","article-title":"The prevalence of polycystic ovaries in women with type 2 diabetes mellitus","volume":"52","author":"Conn","year":"2000","journal-title":"Clin. Endocrinol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"17830","DOI":"10.1074\/jbc.M200186200","article-title":"Loss of the peroxisome proliferation-activated receptor gamma (PPARgamma ) does not affect mammary development and propensity for tumor formation but leads to reduced fertility","volume":"277","author":"Cui","year":"2002","journal-title":"J. Biol. Chem."},{"key":"B14","doi-asserted-by":"publisher","first-page":"D988","DOI":"10.1093\/nar\/gkab1049","article-title":"Ensembl 2022","volume":"50","author":"Cunningham","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"B15","doi-asserted-by":"publisher","first-page":"e1007813","DOI":"10.1371\/journal.pgen.1007813","article-title":"Large-scale genome-wide meta-analysis of polycystic ovary syndrome suggests shared genetic architecture for different diagnosis criteria","volume":"14","author":"Day","year":"2018","journal-title":"PLoS Genet."},{"key":"B16","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.fertnstert.2003.10.004","article-title":"Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome","volume":"81","author":"Eshre","year":"2004","journal-title":"Fertil. Steril."},{"key":"B17","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1530\/REP-18-0027","article-title":"Dysregulated genes and their functional pathways in luteinized granulosa cells from PCOS patients after cabergoline treatment","volume":"155","author":"Ferrero","year":"2018","journal-title":"Reproduction"},{"key":"B18","doi-asserted-by":"publisher","first-page":"2417","DOI":"10.1038\/s41467-019-10310-0","article-title":"Bivariate causal mixture model quantifies polygenic overlap between complex traits beyond genetic correlation","volume":"10","author":"Frei","year":"2019","journal-title":"Nat. Commun."},{"key":"B19","doi-asserted-by":"publisher","first-page":"e1004383","DOI":"10.1371\/journal.pgen.1004383","article-title":"Bayesian test for colocalisation between pairs of genetic association studies using summary statistics","volume":"10","author":"Giambartolomei","year":"2014","journal-title":"PLoS Genet."},{"key":"B20","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/1475-2891-13-17","article-title":"Peroxisome proliferator-activated receptors and their ligands: Nutritional and clinical implications--a review","volume":"13","author":"Grygiel-G\u00f3rniak","year":"2014","journal-title":"Nutr. J."},{"key":"B21","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1093\/nar\/23.2.277","article-title":"High affinity binding sites for the Wilms\u2019 tumour suppressor protein WT1","volume":"23","author":"Hamilton","year":"1995","journal-title":"Nucleic Acids Res."},{"key":"B22","doi-asserted-by":"publisher","first-page":"7502","DOI":"10.1038\/ncomms8502","article-title":"Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations","volume":"6","author":"Hayes","year":"2015","journal-title":"Nat. Commun."},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2018.00045","article-title":"Nutritional stress induced by amino acid starvation results in changes for Slc38 transporters in immortalized hypothalamic neuronal cells and primary cortex cells","volume":"5","author":"Hellsten","year":"2018","journal-title":"Front. Mol. Biosci."},{"key":"B24","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1038\/ng.2477","article-title":"New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism","volume":"45","author":"Horikoshi","year":"2013","journal-title":"Nat. Genet."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1329","DOI":"10.1038\/s41436-020-0803-8","article-title":"DLG2 variants in patients with pubertal disorders","volume":"22","author":"Jee","year":"2020","journal-title":"Genet. Med."},{"key":"B26","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1038\/s41419-021-04016-9","article-title":"The m6A mRNA demethylase FTO in granulosa cells retards FOS-dependent ovarian aging","volume":"12","author":"Jiang","year":"2021","journal-title":"Cell Death Dis."},{"key":"B27","doi-asserted-by":"publisher","first-page":"560","DOI":"10.2337\/dc18-1738","article-title":"The impact of obesity on the incidence of type 2 diabetes among women with polycystic ovary syndrome","volume":"42","author":"Kakoly","year":"2019","journal-title":"Diabetes Care"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1016\/j.fertnstert.2017.09.004","article-title":"Polycystic ovary syndrome is a risk factor for diabetes and prediabetes in middle-aged but not elderly women: A long-term population-based follow-up study","volume":"108","author":"Kazemi Jaliseh","year":"2017","journal-title":"Fertil. Steril."},{"key":"B29","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1016\/j.fertnstert.2006.01.019","article-title":"Prevalence of polycystic ovarian changes and polycystic ovary syndrome in premenopausal women with treated type 2 diabetes mellitus","volume":"86","author":"Kelestimur","year":"2006","journal-title":"Fertil. Steril."},{"key":"B30","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1093\/molehr\/gan082","article-title":"Gene expression microarray profiles of cumulus cells in lean and overweight-obese polycystic ovary syndrome patients","volume":"15","author":"Kenigsberg","year":"2009","journal-title":"Mol. Hum. Reprod."},{"key":"B31","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1038\/ng.2892","article-title":"A general framework for estimating the relative pathogenicity of human genetic variants","volume":"46","author":"Kircher","year":"2014","journal-title":"Nat. Genet."},{"key":"B32","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1007\/s11684-017-0575-y","article-title":"Oxidative stress in granulosa cells contributes to poor oocyte quality and IVF-ET outcomes in women with polycystic ovary syndrome","volume":"12","author":"Lai","year":"2018","journal-title":"Front. Med."},{"key":"B33","doi-asserted-by":"publisher","first-page":"4323","DOI":"10.1093\/hmg\/ddy317","article-title":"Large-scale meta-analysis highlights the hypothalamic-pituitary-gonadal axis in the genetic regulation of menstrual cycle length","volume":"27","author":"Laisk","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"B34","doi-asserted-by":"publisher","first-page":"14956","DOI":"10.1073\/pnas.95.25.14956","article-title":"Evidence for a genetic basis for hyperandrogenemia in polycystic ovary syndrome","volume":"95","author":"Legro","year":"1998","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B36","doi-asserted-by":"publisher","first-page":"240","DOI":"10.4239\/wjd.v13.i3.240","article-title":"Higher risk of type 2 diabetes in young women with polycystic ovary syndrome: A 10-year retrospective cohort study","volume":"13","author":"Liao","year":"2022","journal-title":"World J. Diabetes"},{"key":"B37","doi-asserted-by":"publisher","first-page":"e0230032","DOI":"10.1371\/journal.pone.0230032","article-title":"Common genetic variants in ADCY5 and gestational glycemic traits","volume":"15","author":"Lin","year":"2020","journal-title":"PloS one"},{"key":"B38","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1186\/s12916-022-02238-y","article-title":"Genomic correlation, shared loci, and causal relationship between obesity and polycystic ovary syndrome: A large-scale genome-wide cross-trait analysis","volume":"20","author":"Liu","year":"2022","journal-title":"BMC Med."},{"key":"B39","doi-asserted-by":"publisher","first-page":"6489","DOI":"10.3892\/mmr.2017.7463","article-title":"The role of fructose-1, 6-bisphosphatase 1 in abnormal development of ovarian follicles caused by high testosterone concentration","volume":"16","author":"Liu","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"B40","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1038\/ng.2653","article-title":"The genotype-tissue expression (GTEx) project","volume":"45","author":"Lonsdale","year":"2013","journal-title":"Nat. Genet."},{"key":"B41","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1038\/nrendo.2013.227","article-title":"The bigger picture of FTO\u2014The first GWAS-identified obesity gene","volume":"10","author":"Loos","year":"2014","journal-title":"Nat. Rev. Endocrinol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1505","DOI":"10.1038\/s41588-018-0241-6","article-title":"Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps","volume":"50","author":"Mahajan","year":"2018","journal-title":"Nat. Genet."},{"key":"B43","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1186\/1471-2164-12-151","article-title":"Sequential analysis of global gene expression profiles in immature and in vitro matured bovine oocytes: Potential molecular markers of oocyte maturation","volume":"12","author":"Mamo","year":"2011","journal-title":"BMC Genomics"},{"key":"B44","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1038\/ng.2299","article-title":"Mutations in NNT encoding nicotinamide nucleotide transhydrogenase cause familial glucocorticoid deficiency","volume":"44","author":"Meimaridou","year":"2012","journal-title":"Nat. Genet."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1527","DOI":"10.1038\/s41588-021-00945-5","article-title":"An open approach to systematically prioritize causal variants and genes at all published human GWAS trait-associated loci","volume":"53","author":"Mountjoy","year":"2021","journal-title":"Nat. Genet."},{"key":"B46","doi-asserted-by":"publisher","first-page":"2806","DOI":"10.1210\/en.2011-0207","article-title":"Lack of maternal glutamate cysteine ligase modifier subunit (Gclm) decreases oocyte glutathione concentrations and disrupts preimplantation development in mice","volume":"152","author":"Nakamura","year":"2011","journal-title":"Endocrinology"},{"key":"B47","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.1038\/s41423-019-0266-5","article-title":"CMIP is a negative regulator of T cell signaling","volume":"17","author":"Oniszczuk","year":"2020","journal-title":"Cell. Mol. Immunol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1093\/molehr\/gah247","article-title":"Transcriptome analysis of FSH and FSH variant stimulation in granulosa cells from IVM patients reveals novel regulated genes","volume":"12","author":"Perlman","year":"2006","journal-title":"Mol. Hum. Reprod."},{"key":"B49","doi-asserted-by":"publisher","first-page":"3765","DOI":"10.1210\/jc.2013-1923","article-title":"Mesenchymal stem\/progenitors and other endometrial cell types from women with polycystic ovary syndrome (PCOS) display inflammatory and oncogenic potential","volume":"98","author":"Piltonen","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1894","DOI":"10.1038\/s41591-019-0666-1","article-title":"Prenatal androgen exposure and transgenerational susceptibility to polycystic ovary syndrome","volume":"25","author":"Risal","year":"2019","journal-title":"Nat. Med."},{"key":"B51","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1038\/nature14248","article-title":"Integrative analysis of 111 reference human epigenomes","volume":"518","author":"Roadmap Epigenomics Consortium","year":"2015","journal-title":"Nature"},{"key":"B52","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1038\/ejhg.2015.102","article-title":"Genome-wide association study with 1000 genomes imputation identifies signals for nine sex hormone-related phenotypes","volume":"24","author":"Ruth","year":"2016","journal-title":"Eur. J. Hum. Genet."},{"key":"B53","doi-asserted-by":"publisher","first-page":"533","DOI":"10.18502\/ijrm.v17i8.4818","article-title":"The prevalence of polycystic ovary syndrome in adolescents: A systematic review and meta-analysis","volume":"17","author":"Saei Ghare Naz","year":"2019","journal-title":"Int. J. Reprod. Biomed."},{"key":"B54","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1016\/j.tins.2018.03.011","article-title":"Progress in understanding and treating SCN2A-mediated disorders","volume":"41","author":"Sanders","year":"2018","journal-title":"Trends Neurosci."},{"key":"B55","doi-asserted-by":"publisher","first-page":"15539","DOI":"10.1038\/ncomms15539","article-title":"Meta-analysis identifies five novel loci associated with endometriosis highlighting key genes involved in hormone metabolism","volume":"8","author":"Sapkota","year":"2017","journal-title":"Nat. Commun."},{"key":"B56","doi-asserted-by":"publisher","first-page":"e1003449","DOI":"10.1371\/journal.pgen.1003449","article-title":"All SNPs are not created equal: Genome-wide association studies reveal a consistent pattern of enrichment among functionally annotated SNPs","volume":"9","author":"Schork","year":"2013","journal-title":"PLoS Genet."},{"key":"B57","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1007\/s10815-013-0025-y","article-title":"Peroxisome proliferator activated receptor gamma gene variants influence susceptibility and insulin related traits in Indian women with polycystic ovary syndrome","volume":"30","author":"Shaikh","year":"2013","journal-title":"J. Assist. Reprod. Genet."},{"key":"B58","doi-asserted-by":"publisher","first-page":"e2466","DOI":"10.1371\/journal.pone.0002466","article-title":"Pioglitazone enhances mitochondrial biogenesis and ribosomal protein biosynthesis in skeletal muscle in polycystic ovary syndrome","volume":"3","author":"Skov","year":"2008","journal-title":"PloS one"},{"key":"B59","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1007\/s00439-019-02060-2","article-title":"Discovery of shared genomic loci using the conditional false discovery rate approach","volume":"139","author":"Smeland","year":"2020","journal-title":"Hum. Genet."},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.2202\/1544-6115.1027","article-title":"Linear models and empirical bayes methods for assessing differential expression in microarray experiments","volume":"3","author":"Smyth","year":"2004","journal-title":"Stat. Appl. Genet. Mol. Biol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1095\/biolreprod.111.095885","article-title":"Perivascular human endometrial mesenchymal stem cells express pathways relevant to self-renewal, lineage specification, and functional phenotype.","volume":"86","author":"Spitzer","year":"2012","journal-title":"Biol. Reprod."},{"key":"B62","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1038\/s41574-021-00517-x","article-title":"Epigenetic inheritance of polycystic ovary syndrome \u2014 Challenges and opportunities for treatment","volume":"17","author":"Stener-Victorin","year":"2021","journal-title":"Nat. Rev. Endocrinol."},{"key":"B63","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.1007\/s43032-021-00776-z","article-title":"Mendelian randomization analysis identified potential genes pleiotropically associated with polycystic ovary syndrome","volume":"29","author":"Sun","year":"2022","journal-title":"Reprod. Sci."},{"key":"B64","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1002\/cm.21628","article-title":"The function of SEC22B and its role in human diseases","volume":"77","author":"Sun","year":"2020","journal-title":"Cytoskelet. Hob."},{"key":"B65","doi-asserted-by":"publisher","first-page":"e0247486","DOI":"10.1371\/journal.pone.0247486","article-title":"Impact of polycystic ovary syndrome on quality of life of women in correlation to age, basal metabolic index, education and marriage","volume":"16","author":"Tabassum","year":"2021","journal-title":"PloS one"},{"key":"B66","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/S2213-8587(19)30345-6","article-title":"Diabetes: A metabolic and reproductive disorder in women","volume":"8","author":"Thong","year":"2020","journal-title":"Lancet. Diabetes Endocrinol."},{"key":"B67","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1146\/annurev-genom-091212-153455","article-title":"Major histocompatibility complex genomics and human disease","volume":"14","author":"Trowsdale","year":"2013","journal-title":"Annu. Rev. Genomics Hum. Genet."},{"key":"B68","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1093\/humrep\/deab250","article-title":"Leveraging northern European population history: Novel low-frequency variants for polycystic ovary syndrome","volume":"37","author":"Tyrmi","year":"2022","journal-title":"Hum. Reprod."},{"key":"B69","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/s43586-021-00056-9","article-title":"Genome-wide association studies","volume":"1","author":"Uffelmann","year":"2021","journal-title":"Nat. Rev. Methods Prim."},{"key":"B70","doi-asserted-by":"publisher","first-page":"2100","DOI":"10.1210\/jc.2005-1494","article-title":"Heritability of polycystic ovary syndrome in a Dutch twin-family study","volume":"91","author":"Vink","year":"2006","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"B71","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.1038\/s41588-021-00913-z","article-title":"Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression","volume":"53","author":"V\u00f5sa","year":"2021","journal-title":"Nat. Genet."},{"key":"B72","doi-asserted-by":"publisher","first-page":"e1008720","DOI":"10.1371\/journal.pgen.1008720","article-title":"Eliciting priors and relaxing the single causal variant assumption in colocalisation analyses","volume":"16","author":"Wallace","year":"2020","journal-title":"PLoS Genet."},{"key":"B73","doi-asserted-by":"publisher","first-page":"138","DOI":"10.14715\/cmb\/2019.65.7.24","article-title":"WT1 influences apoptosis and proliferation of immature mice granular cells through regulation of the wnt\/\u00ce\u00b2-catenin signal pathway","volume":"65","author":"Wang","year":"","journal-title":"Cell. Mol. Biol."},{"key":"B74","doi-asserted-by":"publisher","first-page":"116940","DOI":"10.1016\/j.lfs.2019.116940","article-title":"Hyperandrogenemia and insulin resistance: The chief culprit of polycystic ovary syndrome","volume":"236","author":"Wang","year":"","journal-title":"Life Sci."},{"key":"B75","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1159\/000486784","article-title":"Wilms\u2019 tumor 1 overexpression in granulosa cells is associated with polycystic ovaries in polycystic ovary syndrome patients","volume":"83","author":"Wang","year":"2018","journal-title":"Gynecol. Obstet. Invest."},{"key":"B76","doi-asserted-by":"publisher","first-page":"1826","DOI":"10.1038\/s41467-017-01261-5","article-title":"Functional mapping and annotation of genetic associations with FUMA","volume":"8","author":"Watanabe","year":"2017","journal-title":"Nat. Commun."},{"key":"B77","doi-asserted-by":"publisher","first-page":"723243","DOI":"10.1155\/2008\/723243","article-title":"PPARs and female reproduction: Evidence from genetically manipulated mice","volume":"2008","author":"Yang","year":"2008","journal-title":"PPAR Res."},{"key":"B78","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1016\/j.fertnstert.2018.04.024","article-title":"Diabetes mellitus and insulin resistance in mothers, fathers, sisters, and brothers of women with polycystic ovary syndrome: A systematic review and meta-analysis","volume":"110","author":"Yilmaz","year":"2018","journal-title":"Fertil. Steril."},{"key":"B79","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1080\/09513590600733357","article-title":"Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-\u03b3 gene in women with polycystic ovary syndrome","volume":"22","author":"Yilmaz","year":"2006","journal-title":"Gynecol. Endocrinol."},{"key":"B80","doi-asserted-by":"publisher","first-page":"275","DOI":"10.3889\/oamjms.2017.088","article-title":"Association of the Pro12Ala polymorphism with the metabolic parameters in women with polycystic ovary syndrome","volume":"5","author":"Zaki","year":"2017","journal-title":"Open Access Maced. J. Med. Sci."},{"key":"B81","volume-title":"Current issues in endocrinology and metabolism: Polycystic ovary syndrome","author":"Zawadzki","year":"1992"},{"key":"B82","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1038\/ng.3737","article-title":"Identification of context-dependent expression quantitative trait loci in whole blood","volume":"49","author":"Zhernakova","year":"2017","journal-title":"Nat. Genet."},{"key":"B83","doi-asserted-by":"publisher","first-page":"1305","DOI":"10.1007\/s43032-021-00664-6","article-title":"N6-methyladenosine demethylase FTO induces the dysfunctions of ovarian granulosa cells by upregulating flotillin 2","volume":"29","author":"Zhou","year":"2021","journal-title":"Reprod. Sci."},{"key":"B84","doi-asserted-by":"publisher","first-page":"627","DOI":"10.2337\/db20-0800","article-title":"Polycystic ovary syndrome and risk of type 2 diabetes, coronary heart disease, and stroke","volume":"70","author":"Zhu","year":"2021","journal-title":"Diabetes"}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.905716\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T05:06:09Z","timestamp":1661749569000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.905716\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,29]]},"references-count":84,"alternative-id":["10.3389\/fgene.2022.905716"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2022.905716","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,29]]},"article-number":"905716"}}