Zhiwen Jiang, Patrick F Sullivan, Tengfei Li, Bingxin Zhao, Xifeng Wang, Tianyou Luo, Shuai Huang, Peter Y Guan, Jie Chen, Yue Yang, Jason L Stein, Yun Li, Dajiang Liu, Lei Sun, Hongtu Zhu
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The pivotal role of the X-chromosome in the genetic architecture of the human brain.
Genes on the X-chromosome are extensively expressed in the human brain. However, little is known for the X-chromosome's 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-chromosome's role in the human brain, underscoring its contribution to the differences observed in brain structure and functionality between sexes.
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