Science advances · 2025
The X chromosome's influences on the human brain.
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Jiang Zhiwen, Sullivan Patrick F, Li Tengfei, Zhao Bingxin, Wang Xifeng, Luo Tianyou, Huang Shuai, Guan Peter Y, Chen Jie, Yang Yue, Stein Jason L, Li Yun, Liu Dajiang, Sun Lei, Zhu Hongtu
Аннотация
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 networks. We examined 1045 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 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 found 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.