Publication Date

2014

Journal Title

Cell Reports

Abstract

A large portion of common variant loci associated with genetic risk for schizophrenia reside within noncoding sequence of unknown function. Here, we demonstrate promoter and enhancer enrichment in schizophrenia variants associated with expression quantitative trait loci (eQTL). The enrichment is greater when functional annotations derived from the human brain are used relative to peripheral tissues. Regulatory trait concordance analysis ranked genes within schizophrenia genome-wide significant loci for a potential functional role, based on colocalization of a risk SNP, eQTL, and regulatory element sequence. We identified potential physical interactions of noncontiguous proximal and distal regulatory elements. This was verified in prefrontal cortex and -induced pluripotent stem cell-derived neurons for the L-type calcium channel (CACNA1C) risk locus. Our findings point to a functional link between schizophrenia-associated noncoding SNPs and 3D genome architecture associated with chromosomal loopings and transcriptional regulation in the brain.

Volume Number

9

Issue Number

4

Pages

1417-1429

Document Type

Article

EPub Date

2014/12/03

Status

Faculty

Facility

School of Medicine

Primary Department

Molecular Medicine

Additional Departments

General Internal Medicine

PMID

25453756

DOI

10.1016/j.celrep.2014.10.015


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