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First page of Mendelian randomization analyses reveal causal relationships between brain structural connectivity and risk of polycystic ovary syndrome

Background: It is well known that brain structure is affected by sex hormones, and polycystic ovary syndrome(PCOS) is often accompanied by abnormal hormone production. However, the relationship between brain structural connectivity and polycystic ovary syndrome is currently unknown. Methods: Two-sample mendelian randomization (2SMR) was used by searching an appropriate European population genome-wide association studies (GWAS) database of the structural connections of the brain and polycystic ovary syndrome from the Ieu Open GWAS Project database. 206 related brain structural connectivity single-nucleotide polymorphisms (SNPs) were screened as instrumental variables (IVs). Subsequently, we employ various statistical methods including inverse variance weighting (IVW), weighted median method (WME), MR-Egger regression, Simple mode, and Weighted mode to investigate the causal link between the structural connections of the brain and polycystic ovary syndrome. Results: According to the IVW results, it was confirmed that the white matter structural connections between the right hemisphere default mode network and the amygdala are associated with the occurrence of PCOS (odds ratio [OR] = 1.559; 95% confidence interval [CI] = 1.028–2.36; P = 0.037). The white matter structural connectivity between the right-hemisphere somatomotor network and the right-hemisphere limbic network was also linked to the development of PCOS (OR = 1.800; 95% CI = 1.077–3.009; P = 0.025). Additionally, the white matter structural connections from the left hemisphere limbic network to the right hemisphere control network, from the left hemisphere limbic network to the thalamus, from the left hemisphere somatomotor network to the left hemisphere control network, and from the right hemisphere limbic network to the thalamus are negatively correlated with the development of PCOS. Leave-one-out sensitivity analyses and heterogeneity tests were performed, and no horizontal pleiotropy was found. Conclusion: Our results point to a causal relationship between the development of PCOS and the white matter structural connectivity from the right hemisphere default mode network to the amygdala, as well as from the right hemisphere somatomotor network to the right hemisphere limbic network.

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Research Article
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S. Karger AG, Basel
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2025
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