Common variants contribute to intrinsic human brain functional networks.
Bingxin ZhaoTengfei LiStephen M SmithDi XiongXifeng WangYue YangTianyou LuoZiliang ZhuYue ShanNana MatobaQuan SunYuchen YangMads Engel HaubergJaroslav BendlJohn F FullardPanagiotis RoussosWeili LinYun LiJason L SteinHongtu ZhuPublished in: Nature genetics (2022)
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.
Keyphrases
- resting state
- functional connectivity
- white matter
- major depressive disorder
- magnetic resonance
- bipolar disorder
- copy number
- cerebral ischemia
- adipose tissue
- convolutional neural network
- computed tomography
- insulin resistance
- metabolic syndrome
- working memory
- deep learning
- cognitive decline
- machine learning
- drug induced