CORE-Copenhagen Research Centre for Mental Health, Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark.
iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.
Transl Psychiatry. 2022 Aug 16;12(1):334. doi: 10.1038/s41398-022-02068-9.
Autism spectrum disorder (ASD) refers to a group of neurodevelopmental disorders which include deficits in behavior, social interaction and communication. ASD has a complex genetic architecture, and it is also influenced by certain environmental exposures. Both types of predisposing factors may be related to immunological mechanisms, involving, for example, immune system genes and infections. Past studies have shown an association between infections occurring during the pregnancy in the mother and increased risk of ASD in the child, an observation which has received recent support from experimental animal studies of ASD-like behavior. The aim of this study was to study the genetic contribution to this effect. We employed genetic correlation analyses across potential ASD subtypes stratified on the basis of maternal pregnancy-related infections within the iPSYCH ASD case-cohort sample, as well as a case-case GWAS. We validated the trends of the genetic correlation analyses observed in our sample using GWAS summary statistics from the PGC ASD study (excluding iPSYCH). The genetic correlation between ASD with a history of maternal pregnancy-related infections and ASD without a history of maternal infections in iPSYCH was r = 0.3811. We obtained a similar estimate between the former and the PGC ASD phenotype (r = 0.3997). Both estimates are lower compared to the genetic correlation between ASD without a history of maternal infections and the PGC ASD phenotype (r = 0.6735), and between ASD with a history of maternal infections occurring only more than 2 months following childbirth and the PGC ASD phenotype (r = 0.6293). Additionally, we observed genetic variance between the two main ASD phenotypes using summary statistics from the case-case GWAS in iPSYCH (h = 0.1059), indicating genome-wide differences between the phenotypes. Our results suggest potentially different etiologies of ASD based on a history of maternal pregnancy-related infections, which may, in part, be genetic. This highlights the relevance of maternal pregnancy-related infections to genetic studies of ASD and provides new insights into the molecular underpinnings of ASD.
自闭症谱系障碍 (ASD) 是一组神经发育障碍，包括行为、社交互动和沟通方面的缺陷。ASD 具有复杂的遗传结构，也受到某些环境暴露的影响。这两种易感因素可能与免疫机制有关，例如免疫系统基因和感染。过去的研究表明，母亲怀孕期间发生的感染与儿童患 ASD 的风险增加之间存在关联，这一观察结果最近得到了 ASD 样行为的实验动物研究的支持。本研究旨在研究这种效应的遗传贡献。我们在 iPSYCH ASD 病例 - 对照样本中，根据母亲怀孕期间与感染相关的情况，对潜在的 ASD 亚型进行分层，然后进行遗传相关性分析，同时还进行了病例 - 病例 GWAS。我们使用 PGC ASD 研究（不包括 iPSYCH）的 GWAS 汇总统计数据来验证我们样本中遗传相关性分析趋势。iPSYCH 中具有母亲怀孕期间感染史的 ASD 与无母亲感染史的 ASD 之间的遗传相关性为 r=0.3811。我们在前一组和 PGC ASD 表型之间获得了类似的估计值（r=0.3997）。这两个估计值都低于无母亲感染史的 ASD 与 PGC ASD 表型之间的遗传相关性（r=0.6735），也低于仅在儿童出生后 2 个月以上发生母亲感染史的 ASD 与 PGC ASD 表型之间的遗传相关性（r=0.6293）。此外，我们使用 iPSYCH 病例 - 病例 GWAS 的汇总统计数据观察到两种主要 ASD 表型之间的遗传方差（h=0.1059），这表明表型之间存在全基因组差异。我们的结果表明，基于母亲怀孕期间与感染相关的历史，ASD 可能具有不同的病因，这在一定程度上与遗传有关。这突出了母亲怀孕期间与感染相关的情况对 ASD 遗传研究的重要性，并为 ASD 的分子基础提供了新的见解。
Zotero 插件