The X chromosome's influences on the human brain

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

doi:10.1126/sciadv.adq5360

The X chromosome's influences on the human brain

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

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English (US)
Article number	eadq3874
Journal	Science Advances
Volume	11
Issue number	4
DOIs	https://doi.org/10.1126/sciadv.adq5360
State	Published - Jan 24 2025

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title = "The X chromosome's influences on the human brain",

abstract = "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.",

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AU - Sullivan, Patrick F.

AU - Li, Tengfei

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AU - Wang, Xifeng

AU - Luo, Tianyou

AU - Huang, Shuai

AU - Guan, Peter Y.

AU - Chen, Jie

AU - Yang, Yue

AU - Stein, Jason L.

AU - Li, Yun

AU - Liu, Dajiang

AU - Sun, Lei

AU - Zhu, Hongtu

N1 - Publisher Copyright: © 2025 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC ).

PY - 2025/1/24

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The X chromosome's influences on the human brain

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