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
Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Sci Adv. 2025 Jan 24;11(4):eadq5360. doi: 10.1126/sciadv.adq5360.
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.
X染色体上的基因在人类大脑中广泛表达。然而，对于X染色体对大脑解剖结构、微观结构和功能网络的影响却知之甚少。我们研究了英国生物银行中38529名参与者的1045种复杂脑成像特征。我们揭示了潜在的常染色体与X染色体的相互作用，同时提出了一个概述脑成像特征剂量补偿的图谱。通过广泛的关联研究，我们确定了72对全基因组显著的性状-基因座对（包括29个新关联），这些对与脑部相关疾病（尤其是精神分裂症）共享遗传结构。此外，我们发现了独特的性别特异性关联，并评估了性别之间遗传效应的差异。我们的研究为X染色体在人类大脑中的作用提供了关键见解，强调了其对男女大脑结构和功能差异的贡献。
