A Role for Noncoding Variation in Schizophrenia

• DOI: 10.1016/j.celrep.2014.10.015
• Publication Date: 2014-11-06T18:52:23Z
• Authors: Panos Roussos; Amanda C. Mitchell; Georgios Voloudakis; John F. Fullard; Venu M. Pothula; Jonathan Tsang; Eli A. Stahl; Anastasios Georga...; Douglas M. Ruderfer; Alexander Charney; Yukinori Okada; Katherine A. Simi...; Jane Worthington; Leonid Padyukov; Lars Klareskog; Peter K. Gregersen; Robert M. Plenge; Soumya Raychaudhuri; Menachem Fromer; Shaun M. Purcell; Kristen J. Brennand; Nikolaos K. Robakis; Eric E. Schadt; Schahram Akbarian; Pamela Sklar
• Keywords: Genome-wide Association Study

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