Growing evidence suggested that individuals with autism spectrum disorder (ASD) associated with stroke and cardiovascular disease (CVD). However, the causal association between ASD and the risk of stroke and CVD remains unclear. To validate this, we performed two-sample Mendelian randomization (MR) and two-step mediation MR analyses, using relevant genetic variants sourced from the largest genome-wide association studies (GWASs). Two-sample MR evidence indicated causal relationships between ASD and any stroke (OR = 1.1184, 95% CI: 1.0302–1.2142, P < 0.01), ischemic stroke (IS) (OR = 1.1157, 95% CI: 1.0237–1.2160, P = 0.01), large-artery atherosclerotic stroke (LAS) (OR = 1.2902, 95% CI: 1.0395–1.6013, P = 0.02), atrial fibrillation (AF) (OR = 1.0820, 95% CI: 1.0019–1.1684, P = 0.04), and heart failure (HF) (OR = 1.1018, 95% CI: 1.0007–1.2132, P = 0.05). Additionally, two-step mediation MR suggested that type 2 diabetes mellitus (T2DM) partially mediated this effect (OR = 1.14, 95%CI: 1.02–1.28, P = 0.03). The mediated proportion were 10.96% (95% CI: 0.58%–12.10%) for any stroke, 11.77% (95% CI: 10.58%–12.97%) for IS, 10.62% (95% CI: 8.04%–13.20%) for LAS, and 7.57% (95% CI: 6.79%–8.36%) for HF. However, no mediated effect was observed between ASD and AF risk. These findings have implications for the development of prevention strategies and interventions for stroke and CVD in patients with ASD.

中文翻译：

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基因鉴定的介质与自闭症谱系障碍患者中风和心血管疾病风险增加相关


越来越多的证据表明，自闭症谱系障碍 (ASD) 患者与中风和心血管疾病 (CVD) 相关。然而，自闭症谱系障碍（ASD）与中风和心血管疾病风险之间的因果关系仍不清楚。为了验证这一点，我们使用来自最大的全基因组关联研究 (GWAS) 的相关遗传变异进行了两个样本孟德尔随机化 (MR) 和两步中介 MR 分析。两个样本 MR 证据表明 ASD 与任何卒中（OR = 1.1184，95% CI：1.0302–1.2142，P < 0.01）、缺血性卒中 (IS)（OR = 1.1157，95% CI：1.0237–1.2160，P）之间存在因果关系= 0.01）、大动脉粥样硬化性卒中（LAS）（OR = 1.2902，95% CI：1.0395–1.6013，P = 0.02）、心房颤动（AF）（OR = 1.0820，95% CI：1.0019–1.1684，P = 0.04）和心力衰竭（HF）（OR = 1.1018，95% CI：1.0007–1.2132，P = 0.05）。此外，两步中介 MR 表明 2 型糖尿病 (T2DM) 部分介导了这种效应（OR = 1.14，95% CI：1.02–1.28，P = 0.03）。任何卒中的介导比例为 10.96% (95% CI: 0.58%–12.10%)，IS 为 11.77% (95% CI: 10.58%–12.97%)，IS 为 10.62% (95% CI: 8.04%–13.20%)对于 LAS，对于 HF 为 7.57%（95% CI：6.79%–8.36%）。然而，在 ASD 和 AF 风险之间没有观察到中介效应。这些发现对于制定自闭症谱系障碍患者中风和心血管疾病的预防策略和干预措施具有重要意义。