Journal
CELL
Volume 179, Issue 3, Pages 750-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2019.09.021
Keywords
-
Categories
Funding
- NIH [5R37 MH060233, 5R01 MH094714, 1R01 MH110927, R00MH102357, 1F32MH114620]
- National Institute of Neurological Disorders and Stroke of the NIH Training Grant [T32NS048004]
Ask authors/readers for more resources
Tissue-specific regulatory regions harbor substantial genetic risk for disease. Because brain development is a critical epoch for neuropsychiatric disease susceptibility, we characterized the genetic control of the transcriptome in 201 mid-gestational human brains, identifying 7,962 expression quantitative trait loci (eQTL) and 4,635 spliceQTL (sQTL), including several thousand prenatal-specific regulatory regions. We show that significant genetic liability for neuropsychiatric disease lies within prenatal eQTL and sQTL. Integration of eQTL and sQTL with genome-wide association studies (GWAS) via transcriptome-wide association identified dozens of novel candidate risk genes, highlighting shared and stage-specific mechanisms in schizophrenia (SCZ). Gene network analysis revealed that SCZ and autism spectrum disorder (ASD) affect distinct developmental gene co-expression modules. Yet, in each disorder, common and rare genetic variation converges within modules, which in ASD implicates superficial cortical neurons. More broadly, these data, available as a web browser and our analyses, demonstrate the genetic mechanisms by which developmental events have a widespread influence on adult anatomical and behavioral phenotypes.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available