Title

Comprehensive functional genomic resource and integrative model for the human brain

UMMS Affiliation

Program in Bioinformatics and Integrative Biology

Publication Date

2018-12-14

Document Type

Article

Disciplines

Bioinformatics | Computational Biology | Computational Neuroscience | Genetic Phenomena | Genomics | Integrative Biology | Mental Disorders

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.

Keywords

psychiatric disorders, PsychENCODE Consortium, genes, genome

DOI of Published Version

10.1126/science.aat8464

Source

Science. 2018 Dec 14;362(6420). pii: eaat8464. doi: 10.1126/science.aat8464. Link to article on publisher's site

Journal/Book/Conference Title

Science (New York, N.Y.)

Comments

Full author list omitted for brevity. For the full list of authors, see article.

Related Resources

Link to Article in PubMed

PubMed ID

30545857

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