Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap

Science. 2018 Feb 9;359(6376):693-697. doi: 10.1126/science.aad6469.

Abstract

The predisposition to neuropsychiatric disease involves a complex, polygenic, and pleiotropic genetic architecture. However, little is known about how genetic variants impart brain dysfunction or pathology. We used transcriptomic profiling as a quantitative readout of molecular brain-based phenotypes across five major psychiatric disorders-autism, schizophrenia, bipolar disorder, depression, and alcoholism-compared with matched controls. We identified patterns of shared and distinct gene-expression perturbations across these conditions. The degree of sharing of transcriptional dysregulation is related to polygenic (single-nucleotide polymorphism-based) overlap across disorders, suggesting a substantial causal genetic component. This comprehensive systems-level view of the neurobiological architecture of major neuropsychiatric illness demonstrates pathways of molecular convergence and specificity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cerebral Cortex / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Genetic Predisposition to Disease*
  • Humans
  • Mental Disorders / genetics*
  • Multifactorial Inheritance*
  • Nervous System Diseases / genetics*
  • Polymorphism, Single Nucleotide
  • Transcription, Genetic

Grant support