Children with autism spectrum disorder (ASD) have a greater prevalence of gastrointestinal (GI) symptoms than children without ASD. We tested whether polygenic scores for each of three GI disorders (ulcerative colitis, inflammatory bowel disease, and Crohn's disease) were related to GI symptoms in children with and without ASD. Using genotyping data (564 ASD cases and 715 controls) and external genome-wide association study summary statistics, we computed GI polygenic scores for ulcerative colitis (UC-PGS), inflammatory bowel disease (IDB-PGS), and Crohn's disease (CD-PGS). Multivariable logistic regression models, adjusted for genetic ancestry, were used to estimate associations between each GI-PGS and (1) ASD case–control status, and (2) specific GI symptoms in neurotypical children and separately in ASD children. In children without ASD, polygenic scores for ulcerative colitis were significantly associated with experiencing any GI symptom (adjusted odds ratio (aOR) = 1.36, 95% confidence interval (CI) = 1.03–1.81, p = 0.03) and diarrhea specifically (aOR = 5.35, 95% CI = 1.77–26.20, p = 0.01). Among children without ASD, IBD-PGS, and Crohn's PGS were significantly associated with diarrhea (aOR = 3.55, 95% CI = 1.25–12.34, p = 0.02) and loose stools alternating with constipation (aOR = 2.57, 95% CI = 1.13–6.55, p = 0.03), respectively. However, the three PGS were not associated with GI symptoms in the ASD case group. Furthermore, polygenic scores for ulcerative colitis significantly interacted with ASD status on presentation of any GI symptom within a European ancestry subset (aOR = 0.42, 95% CI = 0.19–0.88, p = 0.02). Genetic risk factors for some GI symptoms differ between children with and without ASD. Furthermore, our finding that increased genetic risks for GI inflammatory disorders are associated with GI symptoms in children without ASD informs future work on the early detection of GI disorders.

中文翻译：

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胃肠道炎症性疾病的遗传倾向以及与自闭症和非自闭症儿童胃肠道症状的关联

患有自闭症谱系障碍 (ASD) 的儿童比没有患自闭症谱系障碍 (ASD) 的儿童更容易出现胃肠道 (GI) 症状。我们测试了三种胃肠道疾病（溃疡性结肠炎、炎症性肠病和克罗恩病）的多基因评分是否与患有和不患有自闭症谱系障碍（ASD）儿童的胃肠道症状相关。使用基因分型数据（564 个 ASD 病例和 715 个对照）和外部全基因组关联研究汇总统计数据，我们计算了溃疡性结肠炎 (UC-PGS)、炎症性肠病 (IDB-PGS) 和克罗恩病的 GI 多基因评分疾病（CD-PGS）。根据遗传血统进行调整的多变量逻辑回归模型用于估计每个 GI-PGS 与（1）ASD 病例对照状态和（2）神经典型儿童和 ASD 儿童的特定胃肠道症状之间的关联。在没有 ASD 的儿童中，溃疡性结肠炎的多基因评分与出现任何胃肠道症状显着相关（调整后的比值比 (aOR) = 1.36，95% 置信区间 (CI) = 1.03–1.81，p  = 0.03）和腹泻（aOR = 5.35，95% CI = 1.77–26.20，p = 0.01） 。在无 ASD 的儿童中，IBD-PGS 和克罗恩病 PGS 与腹泻显着相关（aOR = 3.55，95% CI = 1.25–12.34，p = 0.02）和稀便与便秘交替（aOR = 2.57，95% CI = 1.13–6.55，p = 0.03）。然而，这三种 PGS 与 ASD 病例组中的胃肠道症状无关。此外，溃疡性结肠炎的多基因评分与欧洲血统亚群中出现任何胃肠道症状时的 ASD 状态显着相互作用（aOR = 0.42，95% CI = 0.19–0.88，p  = 0.02)。一些胃肠道症状的遗传风险因素在患有自闭症谱系障碍和未患有自闭症谱系障碍的儿童之间有所不同。此外，我们发现胃肠道炎症性疾病的遗传风险增加与无自闭症谱系障碍儿童的胃肠道症状相关，这为未来早期检测胃肠道疾病的工作提供了信息。