{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T17:42:04Z","timestamp":1757612524546,"version":"3.44.0"},"reference-count":46,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T00:00:00Z","timestamp":1755648000000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100017686","name":"Fujian Provincial Health Technology Project","doi-asserted-by":"publisher","award":["2024GGA032"],"award-info":[{"award-number":["2024GGA032"]}],"id":[{"id":"10.13039\/501100017686","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Mitochondrial DNA copy number (mtDNA\u2010CN) has been implicated in gestational metabolic disorders (GMD), yet their causal relationships remain unclear. This study employed genetic approaches to investigate potential causal associations between mtDNA\u2010CN and various GMDs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a two\u2010sample Mendelian randomization (MR) analysis utilizing genome\u2010wide association study (GWAS) summary statistics from large\u2010scale populations: mtDNA\u2010CN (<jats:italic>n<\/jats:italic>\u00a0=\u00a0395\u00a0718), preeclampsia (PE) (<jats:italic>n<\/jats:italic>\u00a0=\u00a0267\u00a0242), gestational diabetes mellitus (GDM) (<jats:italic>n<\/jats:italic>\u00a0=\u00a0123\u00a0579), gestational hypertension (GH) (<jats:italic>n<\/jats:italic>\u00a0=\u00a0118\u00a0990), hyperlipidemia (<jats:italic>n<\/jats:italic>\u00a0=\u00a09714), and obesity (<jats:italic>n<\/jats:italic>\u00a0=\u00a0463\u00a0010). Independent single\u2010nucleotide polymorphisms (SNPs) were rigorously selected as instrumental variables (IVs) following stringent criteria. The primary analysis employed the fixed\u2010effects inverse variance weighted (IVW) method. Multiple sensitivity analyses, including leave\u2010one\u2010out analysis, Cochran's Q test, and MR\u2010Egger regression, were conducted to assess the robustness of our findings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The IVW analysis revealed a significant protective association between increased mtDNA\u2010CN and PE risk (OR\u00a0=\u00a00.6262, 95% CI: 0.4201\u20130.9335, <jats:italic>p\u00a0<\/jats:italic>=\u00a00.0283). However, no significant associations were observed between mtDNA\u2010CN and other GMDs (all <jats:italic>p\u00a0<\/jats:italic>&gt;\u00a00.05). Sensitivity analyses, including MR\u2010Egger regression, showed no evidence of horizontal pleiotropy (all <jats:italic>p<\/jats:italic>\u00a0&gt;\u00a00.05), supporting the robustness of our findings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This genetic investigation provides compelling evidence for a potentially protective effect of higher mtDNA\u2010CN against PE development. These findings not only suggest mtDNA\u2010CN as a promising biomarker for PE risk assessment but also offer novel insights into the biological mechanisms underlying PE, potentially informing future preventive strategies and therapeutic interventions.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.70144","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T14:05:01Z","timestamp":1755698701000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mitochondrial DNA Copy Number and Risk of Gestational Metabolic Disorders: A Two\u2010Sample Mendelian Randomization Study"],"prefix":"10.1111","volume":"94","author":[{"given":"Feng","family":"Zhan","sequence":"first","affiliation":[{"name":"College of Engineering Fujian Jiangxia University  Fuzhou Fujian China"},{"name":"School of Electronic Information Engineering Taiyuan University of Science and Technology  Taiyuan Shanxi 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