Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Jillian R. Haney, CommonMind Consortium, PsychENCODE Consortium, iPSYCH-BROAD Working Group

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.

OriginalsprogEngelsk
TidsskriftScience
Vol/bind359
Udgave nummer6376
Sider (fra-til)693-697
Antal sider5
ISSN0036-8075
DOI
StatusUdgivet - 9 feb. 2018

ID: 199177196