Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Medical Genomics Center, Nagoya University Hospital, Nagoya, Japan.
Int Rev Psychiatry. 2022 Feb 17;34(2):154-167. doi: 10.1080/09540261.2022.2072193. Epub 2022 May 12.
Chromatin remodelling is an important process in neural development and is related to autism spectrum disorder (ASD) and schizophrenia (SCZ) aetiology. To further elucidate the involvement of chromatin remodelling genes in the genetic aetiology of ASD and SCZ in the Japanese population, we performed a case-control study. Targeted sequencing was conducted on coding regions of four BAF chromatin remodelling complex genes: and in 185 ASD, 432 SCZ patients, and 517 controls. 27 rare non-synonymous variants were identified in ASD and SCZ patients, including 25 missense, one in-frame deletion in and one frame-shift variant in . Association analysis was conducted to investigate the burden of rare variants in BAF genes in ASD and SCZ patients. Significant enrichment of rare missense variants in BAF genes, but not synonymous variants, was found in ASD compared to controls. Rare pathogenic variants indicated by tools were significantly enriched in ASD, but not statistically significant in SCZ. Pathogenic-predicted variants were located in disordered binding regions and may confer risk for ASD and SCZ by disrupting protein-protein interactions. Our study supports the involvement of rare missense variants of BAF genes in ASD and SCZ susceptibility.
染色质重塑是神经发育过程中的一个重要过程，与自闭症谱系障碍 (ASD) 和精神分裂症 (SCZ) 的发病机制有关。为了进一步阐明染色质重塑基因在日本人群中 ASD 和 SCZ 的遗传发病机制中的作用，我们进行了病例对照研究。对四个 BAF 染色质重塑复合物基因的编码区域进行了靶向测序： 和 ，包括 185 名 ASD 患者、432 名 SCZ 患者和 517 名对照者。在 ASD 和 SCZ 患者中发现了 27 个罕见的非同义变异，包括 25 个错义变异、一个 在 中的框内缺失和一个 在 中的移码变异。进行了关联分析，以研究 BAF 基因中罕见变异在 ASD 和 SCZ 患者中的负担。与对照组相比，在 ASD 中发现了 BAF 基因中罕见错义变异的显著富集，但在 SCZ 中没有统计学意义。由 工具指示的致病性变异在 ASD 中显著富集，但在 SCZ 中没有统计学意义。致病性预测的变异位于无序结合区域，可能通过破坏蛋白质-蛋白质相互作用而导致 ASD 和 SCZ 的风险。我们的研究支持 BAF 基因的罕见错义变异在 ASD 和 SCZ 易感性中的作用。
