{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T02:36:17Z","timestamp":1790044577040,"version":"4.0.1"},"reference-count":83,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T00:00:00Z","timestamp":1753315200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T00:00:00Z","timestamp":1753315200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFC2705503"],"award-info":[{"award-number":["2023YFC2705503"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl J Gynecology &amp; Obste"],"published-print":{"date-parts":[[2026,1]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n Polycystic ovary syndrome (PCOS) is among the most common endocrine and metabolic disorders. Kisspeptin, a neuropeptide, which has been implicated in enhancing hypothalamic\u2013pituitary\u2013ovarian (HPO) axis activity, might play a role in the pathogenesis of PCOS. However, previous studies have had inconsistent results.<\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n In this study, we conducted meta\u2010analyses to assess the possible association between kisspeptin hormone and its genetic aspect with PCOS. Additionally, we performed a Mendelian randomization (MR) analysis to clarify the cause\u2013effect relationship of kisspeptin level and the risk of developing PCOS.<\/jats:p>\n <\/jats:sec>\n \n Search Strategy<\/jats:title>\n We obtained summary data from published clinical studies and genome\u2010wide association study (GWAS) consortia studies to perform meta\u2010analyses and an MR study. A literature search for eligible studies published until December 2023 was performed. Exposure SNPs for kisspeptin level were derived from a GWAS dataset from the deCODE database, while the genetic associations for PCOS were obtained from the FinnGen study and the largest GWAS dataset.<\/jats:p>\n <\/jats:sec>\n \n Selection Criteria<\/jats:title>\n \n Studies that evaluated the association between the kisspeptin level and\/or\n KiSS\u20101 metastasis suppressor<\/jats:italic>\n (\n KISS1<\/jats:italic>\n ) polymorphisms and PCOS were included for meta\u2010analyses.\n <\/jats:p>\n <\/jats:sec>\n \n Data Collection and Analysis<\/jats:title>\n \n Data extraction was performed, and the quality of the studies was assessed using the Newcastle\u2013Ottawa Scale independently by two reviewers. A random\u2010effect model was used to estimate outcomes, and effects were reported as standardized mean difference (SMD) and their 95% confidence interval (CI). The\n I<\/jats:italic>\n 2<\/jats:sup>\n was used to assess heterogeneity. The causal associations between kisspeptin level and PCOS were assessed using MR methods. The reliability, potential biases, and heterogeneity of the results were assessed through inverse variance weighting, MR\u2010Egger regression, Mendelian randomization pleiotropy residual sum and outlier, as well as leave\u2010one\u2010out analysis.\n <\/jats:p>\n <\/jats:sec>\n \n Main Results<\/jats:title>\n \n The meta\u2010analyses incorporated 30 studies that met the criteria. A total of 1932 PCOS patients and 1641 controls were included to analyze the relationship between kisspeptin levels and PCOS. Compared with controls, patients with PCOS showed significantly increased kisspeptin levels (SMD\u2009=\u20090.67, 95% CI [0.36, 0.97],\n P<\/jats:italic>\n \u2009<\u20090.001). The cumulative meta\u2010analysis suggested the result was robust. A total of 872 PCOS and 934 controls were included to assess the association between\n KISS1<\/jats:italic>\n polymorphism and the risk of PCOS. The polymorphisms of rs4889, rs12998, and rs372790354 were significantly associated with PCOS susceptibility. Concretely, rs4889\n KISS1<\/jats:italic>\n gene polymorphism was related to PCOS for the comparisons of allele, homozygote, heterozygote, dominant, and recessive models. The rs12998\n KISS1<\/jats:italic>\n gene polymorphism was associated with the risk of PCOS for the comparisons of homozygote and recessive models. Furthermore, the rs372790354\n KISS1<\/jats:italic>\n gene polymorphism was associated with the risk of PCOS for the comparisons of allele, homozygote, and recessive models. The inverse variance weighted (IVW) method results showed that a higher kisspeptin level was causally related to the risk of PCOS (Finngen) (OR\n IVW<\/jats:sub>\n \u2009=\u20091.12, 95% CI [1.03, 1.22],\n P<\/jats:italic>\n \u2009=\u20090.0065). Finally, the leave\u2010one\u2010out sensitivity analysis corroborated the robustness of the MR findings.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n There is a causal relationship between higher kisspeptin levels and an increased risk of PCOS. rs4889, rs12998, and rs372790354\n KISS1<\/jats:italic>\n gene polymorphisms are associated with the risk of PCOS to varying degrees.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/ijgo.70411","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T11:52:08Z","timestamp":1753357928000},"page":"383-395","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Associations between kisspeptin hormone level and its genetic polymorphisms with polycystic ovary syndrome"],"prefix":"10.1002","volume":"172","author":[{"given":"Ziyi","family":"Zheng","sequence":"first","affiliation":[{"name":"Reproductive Medicine Center The First Affiliated 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