Objective

To identify whether there exists a genetic correlation and causal relationship between 25(OH)D and autism spectrum disorder (ASD).

Methods

Based on large-scale genome-wide association studies, a series of genetic approaches were adopted to obtain summary statistics. Using linkage disequilibrium score regression, we assessed the shared polygenic structure between traits and performed pleiotropic analysis under composite null hypothesis (PLACO) to identify pleiotropic loci between complex traits. A bidirectional Mendelian randomization (MR) analysis was applied to investigate whether there is a causal relationship between 25(OH)D and ASD.

Results

The linkage disequilibrium score regression (LDSC) showed a negative genetic correlation between 25(OH)D and ASD (r_g = − 0.227, P < 0.05), and PLACO analysis identified 20 independent pleiotropic loci matched to 24 pleiotropic genes, of which the function reveals an underlying mechanism on 25(OH)D and ASD. In Mendelian randomization analysis, the inverse variance-weighted (IVW) method with OR = 0.941 (0.796, 1.112) and p < 0.474 did not show a causal relationship between 25(OH)D and ASD, while, in the reverse Mendelian randomization analysis, IVW method showed OR = 1.042 (0.930, 1.169), indicating no causal relationship either.

Conclusion

This study provides evidence for a shared genetic overlap between 25(OH)D and ASD. Bidirectional MR analysis also did not show a definite causal relationship between 25(OH)D and ASD.

中文翻译：

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25(OH) 维生素 D 和自闭症谱系障碍：遗传重叠和因果关系

客观的

确定 25(OH)D 与自闭症谱系障碍 (ASD) 之间是否存在遗传相关性和因果关系。

方法

基于大规模的全基因组关联研究，采用了一系列遗传方法来获得汇总统计数据。使用连锁不平衡评分回归，我们评估了性状之间的共享多基因结构，并在复合零假设 (PLACO) 下进行多效性分析，以确定复杂性状之间的多效位点。应用双向孟德尔随机化 (MR) 分析来研究 25(OH)D 与 ASD 之间是否存在因果关系。

结果

连锁不平衡评分回归 (LDSC) 显示 25(OH)D 和 ASD 之间呈负相关（r _g = − 0.227，P < 0.05），PLACO 分析确定了 20 个独立的多效位点与 24 个多效基因匹配，其中功能揭示了 25(OH)D 和 ASD 的潜在机制。在孟德尔随机化分析中，OR = 0.941 (0.796, 1.112) 和p < 0.474的逆方差加权 (IVW) 方法 未显示 25(OH)D 与 ASD 之间存在因果关系，而在逆向孟德尔随机化分析中, IVW 方法显示 OR = 1.042 (0.930, 1.169)，表明也没有因果关系。

结论

这项研究为 25(OH)D 和 ASD 之间的共享遗传重叠提供了证据。双向 MR 分析也未显示 25(OH)D 与 ASD 之间存在明确的因果关系。