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Comprehensive functional genomic resource and integrative model for the human brain.

Authors
  • Wang, Daifeng
  • Liu, Shuang
  • Warrell, Jonathan
  • Won, Hyejung
  • Shi, Xu
  • Navarro, Fabio CP
  • Clarke, Declan
  • Gu, Mengting
  • Emani, Prashant
  • Yang, Yucheng T
  • Xu, Min
  • Gandal, Michael J
  • Lou, Shaoke
  • Zhang, Jing
  • Park, Jonathan J
  • Yan, Chengfei
  • Rhie, Suhn Kyong
  • Manakongtreecheep, Kasidet
  • Zhou, Holly
  • Nathan, Aparna
  • And 21 more
Publication Date
Dec 01, 2018
Source
eScholarship - University of California
Keywords
License
Unknown
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Abstract

Despite progress in defining genetic risk for psychiatric disorders, their molecular mechanisms remain elusive. Addressing this, the PsychENCODE Consortium has generated a comprehensive online resource for the adult brain across 1866 individuals. The PsychENCODE resource contains ~79,000 brain-active enhancers, sets of Hi-C linkages, and topologically associating domains; single-cell expression profiles for many cell types; expression quantitative-trait loci (QTLs); and further QTLs associated with chromatin, splicing, and cell-type proportions. Integration shows that varying cell-type proportions largely account for the cross-population variation in expression (with >88% reconstruction accuracy). It also allows building of a gene regulatory network, linking genome-wide association study variants to genes (e.g., 321 for schizophrenia). We embed this network into an interpretable deep-learning model, which improves disease prediction by ~6-fold versus polygenic risk scores and identifies key genes and pathways in psychiatric disorders.

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