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

Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap.

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.

PMID:
29439242
PMCID:
PMC5898828
DOI:
10.1126/science.aad6469
[Indexed for MEDLINE]
Free PMC Article

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