{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:26:38Z","timestamp":1753889198265,"version":"3.41.2"},"reference-count":67,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T00:00:00Z","timestamp":1722816000000},"content-version":"vor","delay-in-days":217,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Depression and Anxiety"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:p>This research has suggested a link between major depressive disorder (MDD) and infertility, with interleukin\u201018 (IL\u201018) being proposed as a potential mediator due to its connections to both conditions. A Mendelian randomization (MR) approach was utilized in this study, which drew on genetic data from 500,199 European participants studied for MDD, along with additional IL\u201018 and reproductive health data from the FinnGen consortium and GWAS datasets. Single nucleotide polymorphisms were employed as instrumental variables to examine the causal relationships between MDD, genetically predicted IL\u201018 levels, and infertility. In our study, bidirectional MR analysis revealed a significant inverse causal relationship between MDD and genetically predicted IL\u201018 levels, with a higher genetic predisposition to MDD, correlating with reduced IL\u201018 levels (<jats:italic>\u03b2<\/jats:italic>: \u22120.40; 95% confidence interval (CI): \u22120.69 to \u22120.11; <jats:italic>P<\/jats:italic>\u2009=\u20097.09\u2009\u00d7\u200910<jats:sup>\u22123<\/jats:sup>). Additionally, MDD is found to significantly increase the risk of female infertility. Notably, genetically predicted IL\u201018 levels demonstrated a protective effect against female infertility (odds ratio (OR): 0.92; 95% CI: 0.86\u20130.98; <jats:italic>P<\/jats:italic>\u2009=\u20091.17\u2009\u00d7\u200910<jats:sup>\u22122<\/jats:sup>). Mediation analysis indicated that genetically predicted IL\u201018 levels partially mediated the impact of MDD on female infertility associated with cervical, vaginal, other or unspecified origin, accounting for up to 14.61% of this effect. No evidence of pleiotropy or heterogeneity was detected. The role of genetic predispositions to MDD in influencing genetically predicted IL\u201018 levels, and subsequently, female infertility, was highlighted by our study, offering insights into the complex interplay between mental health and reproductive biology. These findings contribute to a deeper understanding of the genetic and molecular pathways influencing these conditions, suggesting new directions for research and potential therapeutic interventions.<\/jats:p>","DOI":"10.1155\/2024\/9234876","type":"journal-article","created":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T11:48:14Z","timestamp":1722858494000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Perspective Exploring Novel Associations of IL\u201018 Levels as a Mediator of the Causal Links between Major Depression and Reproductive 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