A Transcriptomic Atlas of the Human Brain Reveals Genetically Determined Aspects of Neuropsychiatric Health

Abstract

Imaging features associated with neuropsychiatric traits can provide valuable insights into underlying pathophysiology. Using data from the UK biobank, we perform tissue-specific TWAS on over 3,500 neuroimaging phenotypes to generate a publicly accessible resource detailing the neurophysiologic consequences of gene expression. As a comprehensive catalog of neuroendophenotypes, this resource represents a powerful neurologic gene prioritization schema that can improve our understanding of brain function, development, and disease. We show that our approach generates reproducible results in internal and external replication datasets. Notably, genetically determined expression alone is shown here to enable high-fidelity reconstruction of brain structure and organization. We demonstrate complementary benefits of cross-tissue and single-tissue analyses towards an integrated neurobiology and provide evidence that gene expression outside the central nervous system provides unique insights into brain health. As an application, we show that over 40% of genes previously associated with schizophrenia in the largest GWAS meta-analysis causally affect neuroimaging phenotypes noted to be altered in schizophrenic patients.