Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
---|---|
Journal | Science |
Volume | 359 |
Issue number | 6376 |
Pages (from-to) | 693-697 |
Number of pages | 5 |
ISSN | 0036-8075 |
DOIs | |
Publication status | Published - 9 Feb 2018 |
ID: 199177196