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The pivotal role of the X-chromosome in the genetic architecture of the human brain

Jiang, Z.; Sullivan, P. F.; Li, T.; Zhao, B.; Wang, X.; Luo, T.; Huang, S.; Guan, P. Y.; Chen, J.; Yang, Y.; Stein, J. L.; Li, Y.; Liu, D.; Sun, L.; Zhu, H.

2023-09-01 genetic and genomic medicine
10.1101/2023.08.30.23294848 medRxiv
Show abstract

Genes on the X-chromosome are extensively expressed in the human brain. However, little is known for the X-chromosomes impact on the brain anatomy, microstructure, and functional network. We examined 1,045 complex brain imaging traits from 38,529 participants in the UK Biobank. We unveiled potential autosome-X-chromosome interactions, while proposing an atlas outlining dosage compensation (DC) for brain imaging traits. Through extensive association studies, we identified 72 genome-wide significant trait-locus pairs (including 29 new associations) that share genetic architectures with brain-related disorders, notably schizophrenia. Furthermore, we discovered unique sex-specific associations and assessed variations in genetic effects between sexes. Our research offers critical insights into the X-chromosomes role in the human brain, underscoring its contribution to the differences observed in brain structure and functionality between sexes. One-sentence SummaryWe investigated the genetic impact of the X-chromosome and the sex differences in the human brain.

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