Common variants contribute to intrinsic human brain functional networks

Bingxin Zhao, Tengfei Li, Stephen M. Smith, Di Xiong, Xifeng Wang, Yue Yang, Tianyou Luo, Ziliang Zhu, Yue Shan, Nana Matoba, Quan Sun, Yuchen Yang, Mads E. Hauberg, Jaroslav Bendl, John F. Fullard, Panagiotis Roussos, Weili Lin, Yun Li, Jason L. Stein, Hongtu Zhu

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

The human brain forms functional networks of correlated activity, which have been linked with both cognitive and clinical outcomes. However, the genetic variants affecting brain function are largely unknown. Here, we used resting-state functional magnetic resonance images from 47,276 individuals to discover and validate common genetic variants influencing intrinsic brain activity. We identified 45 new genetic regions associated with brain functional signatures (P < 2.8 × 10−11), including associations to the central executive, default mode, and salience networks involved in the triple-network model of psychopathology. A number of brain activity-associated loci colocalized with brain disorders (e.g., the APOE ε4 locus with Alzheimer’s disease). Variation in brain function was genetically correlated with brain disorders, such as major depressive disorder and schizophrenia. Together, our study provides a step forward in understanding the genetic architecture of brain functional networks and their genetic links to brain-related complex traits and disorders.

Original languageEnglish
Pages (from-to)508-517
Number of pages10
JournalNature Genetics
Volume54
Issue number4
DOIs
StatePublished - Apr 2022

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