The genetic architecture of the corpus callosum and its genetic overlap with common neuropsychiatric diseases

Si-Jia Chen; Bang-Sheng Wu; Yi-Jun Ge; Shi-Dong Chen; Ya-Nan Ou; Qiang Dong; Jianfeng Feng; Wei Cheng; Jin-Tai Yu

doi:10.1016/j.jad.2023.05.002

The genetic architecture of the corpus callosum and its genetic overlap with common neuropsychiatric diseases

J Affect Disord. 2023 Aug 15:335:418-430. doi: 10.1016/j.jad.2023.05.002. Epub 2023 May 8.

Authors

Si-Jia Chen¹, Bang-Sheng Wu¹, Yi-Jun Ge², Shi-Dong Chen¹, Ya-Nan Ou², Qiang Dong¹, Jianfeng Feng³, Wei Cheng⁴, Jin-Tai Yu⁵

Affiliations

¹ 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.
² Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.
³ Institute of Science and Technology for Brain-inspired Intelligence, Fudan University, Shanghai, China; Department of Computer Science, University of Warwick, Coventry CV4 7AL, UK.
⁴ Institute of Science and Technology for Brain-inspired Intelligence, Fudan University, Shanghai, China; Department of Computer Science, University of Warwick, Coventry CV4 7AL, UK. Electronic address: wcheng@fudan.edu.cn.
⁵ 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. Electronic address: jintai_yu@fudan.edu.cn.

PMID: 37164063
DOI: 10.1016/j.jad.2023.05.002

Abstract

Background: 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.

Methods: 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.

Results: We identified a total of 36 and 82 significant genomic loci for CC FA and volume (P < 5 × 10^-8). 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.

Discussion: 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.

Keywords: Brain diseases; Corpus callosum; Genome-wide association analysis; Neuroimaging; UK Biobank.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anisotropy
Corpus Callosum* / diagnostic imaging
Diffusion Tensor Imaging
Genome-Wide Association Study
Humans
Magnetic Resonance Imaging
White Matter* / diagnostic imaging