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 [F] Diseases Research  / PubMed Research Articles  /
Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap.




Science (New York, N.Y.) Feb ; 359(6376)


Gandal MJ1; Haney JR2; Parikshak NN3; Leppa V4; Ramaswami G5; Hartl C6; Schork AJ7; Appadurai V8; Buil A9; Werge TM10; Liu C11; White KP12; CommonMind Consortium13; PsychENCODE Consortium14; iPSYCH-BROAD Working Group15; Horvath S16; Geschwind DH17;

Author Information


    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.

    Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.




    Publication Type: Journal Article

    This article is licensed under the the National Library of Medicine License. It uses material from the PubMed National Library of Medicine Data.

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