Li Weilin, He Xiaoyu, Tan Chao, Zhang Tao
Department of Anorectal Surgery, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China.
Department of Hematology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
Am J Med Genet B Neuropsychiatr Genet. 2025 Mar;198(2):e33012. doi: 10.1002/ajmg.b.33012. Epub 2024 Oct 1.
Patients with autism spectrum disorder (ASD) are often accompanied by inflammatory bowel disease (IBD) in observational research; however, the potential causal link between the two conditions remains unknown. In this study, we used a two-sample bidirectional Mendelian randomization (MR) approach to assess the causal relationship between ASD and IBD and its main subtypes, Crohn's disease (CD), and ulcerative colitis (UC). Independent genetic instruments from a genome-wide association study (GWAS) for IBD (25,042 cases and 34,915 controls) were used to investigate the association of IBD with ASD data obtained from the PGC and the iPSYCH consortia (N = 46,351). The primary analysis employed the random effects inverse variance weighting (IVW) method. Horizontal pleiotropy was detected using the MR Egger regression and the MR-pleiotropy residual sum and outlier (MR-PRESSO) analysis while heterogeneity was detected using Cochran's Q. The IVW method indicated a positive causal relationship of IBD with ASD (odds ratio (OR) = 1.028, 95% confidence interval (CI) = 1.001-1.056, p = 0.042). In subtype analyses, CD was positively related to ASD (OR = 1.036; 95% CI = 1.004-1.069; p = 0.02); however, UC showed no relationship (OR = 1.021; 95% CI = 0.999-1.044; p = 0.065). In contrast, no evidence of a causal relationship between ASD and IBD or its subtypes (p > 0.05) was found. Our findings provided evidence in support of potential causal associations between IBD/CD and ASD.
在观察性研究中，自闭症谱系障碍（ASD）患者常伴有炎症性肠病（IBD）；然而，这两种疾病之间的潜在因果关系仍不清楚。在本研究中，我们采用两样本双向孟德尔随机化（MR）方法来评估ASD与IBD及其主要亚型克罗恩病（CD）和溃疡性结肠炎（UC）之间的因果关系。来自炎症性肠病全基因组关联研究（GWAS）（25,042例病例和34,915例对照）的独立遗传工具，用于研究炎症性肠病与从PGC和iPSYCH联盟获得的自闭症谱系障碍数据（N = 46,351）之间的关联。主要分析采用随机效应逆方差加权（IVW）方法。使用MR Egger回归和MR多效性残差和异常值（MR-PRESSO）分析检测水平多效性，同时使用Cochran's Q检测异质性。IVW方法表明炎症性肠病与自闭症谱系障碍之间存在正向因果关系（优势比（OR）= 1.028，95%置信区间（CI）= 1.001-1.056，p = 0.042）。在亚型分析中，克罗恩病与自闭症谱系障碍呈正相关（OR = 1.036；95% CI = 1.004-1.069；p = 0.02）；然而，溃疡性结肠炎未显示出相关性（OR = 1.021；95% CI = 0.999-1.044；p = 0.065）。相反，未发现自闭症谱系障碍与炎症性肠病或其亚型之间存在因果关系的证据（p > 0.05）。我们的研究结果为炎症性肠病/克罗恩病与自闭症谱系障碍之间的潜在因果关联提供了证据支持。
