PT  - JOURNAL ARTICLE
AU  - Paul W. Hook
AU  - Andrew S. McCallion
TI  - Heritability enrichment in open chromatin reveals cortical layer contributions to schizophrenia
AID  - 10.1101/427484
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 427484
4099  - http://biorxiv.org/content/early/2018/09/26/427484.short
4100  - http://biorxiv.org/content/early/2018/09/26/427484.full
AB  - Chromatin regions from discrete mouse cell populations predict schizophrenia functional variants and cells wherein they act.Abstract Genome-wide association studies have implicated thousands of non-coding variants across common human phenotypes. However, these studies provide no direct information regarding the cellular context in which disease-associated variants act. We applied stratified linkage disequilibrium score regression to open chromatin signatures from mouse cell populations and evaluated their relationship to 18 phenotypes, emphasizing schizophrenia. We demonstrate signatures from discrete subpopulations of cortical excitatory and inhibitory neurons are significantly enriched for schizophrenia heritability along with retinal cone populations. Enrichment is maximal in features derived from cortical layer V excitatory neurons. These enrichment patterns are iterated across other neuropsychiatric and behavioral phenotypes. We use these data to predict functional variants at 92/144 established schizophrenia loci and further identify the cellular context in which they may modulate risk.