Department of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, China.
Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.
J Affect Disord. 2023 Aug 15;335:418-430. doi: 10.1016/j.jad.2023.05.002. Epub 2023 May 8.
The corpus callosum (CC) is the main structure transferring information between the cerebral hemispheres. Although previous large-scale genome-wide association study (GWAS) has illustrated the genetic architecture of white matter integrity of CC, CC volume is less stressed.
Using MRI data from 33,861 individuals in UK Biobank, we conducted univariate and multivariate GWAS for CC fractional anisotropy (FA) and volume with PLINK 2.0 and MOSTest. All discovered SNPs in the multivariate framework were functionally annotated in FUMA v1.3.8. In the meanwhile, a series of gene property analyses was conducted simultaneously. In addition, we estimated genetic relationship between CC metrics and other neuropsychiatric traits and diseases.
We identified a total of 36 and 82 significant genomic loci for CC FA and volume (P < 5 × 10). And 53 and 27 genes were respectively mapped by four mapping strategies. For CC volume, gene-set analysis revealed pathways mainly relating to cell migration; cell-type analysis found the top enrichment in neuroglia while for CC FA in GABAergic neurons. Furthermore, we found a lot of genetic overlap and shared loci between CC FA and volume and common neuropsychiatric diseases.
Collectively, this study helps to better understand the genetic architecture of whole CC and CC subregions. However, the way to divide CC FA and volume in our study restricts the interpretations of our results. Future work will be needed to pay attention to the genetic structure of white matter volume, and an appropriate division of CC may help to better understand CC structure.
胼胝体（CC）是大脑半球之间传递信息的主要结构。尽管之前的大规模全基因组关联研究（GWAS）已经说明了 CC 白质完整性的遗传结构，但 CC 体积的研究相对较少。
我们使用 UK Biobank 中 33861 个人的 MRI 数据，使用 PLINK 2.0 和 MOSTest 对 CC 分数各向异性（FA）和体积进行单变量和多变量 GWAS。在多变量框架中发现的所有 SNP 在 FUMA v1.3.8 中进行了功能注释。同时，还进行了一系列基因属性分析。此外，我们还估计了 CC 指标与其他神经精神特征和疾病之间的遗传关系。
我们总共确定了 36 个和 82 个 CC FA 和体积的显著基因组位置（P < 5 × 10）。并且通过四种映射策略分别映射了 53 个和 27 个基因。对于 CC 体积，基因集分析显示途径主要与细胞迁移有关；细胞类型分析发现神经胶质细胞中存在最高的富集，而对于 CC FA 则存在于 GABA 能神经元中。此外，我们发现 CC FA 和体积与常见神经精神疾病之间存在大量的遗传重叠和共同的遗传位点。
总的来说，这项研究有助于更好地了解整个 CC 和 CC 子区域的遗传结构。然而，我们研究中 CC FA 和体积的划分方式限制了我们结果的解释。未来的工作将需要关注白质体积的遗传结构，并且 CC 的适当划分可能有助于更好地理解 CC 结构。
