期刊
CELL REPORTS
卷 9, 期 4, 页码 1417-1429出版社
CELL PRESS
DOI: 10.1016/j.celrep.2014.10.015
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资金
- NIH/National Institute of Mental Health (NIMH) grant [R01MH095034]
- NIMH grant [R01MH097276, U01MH103392, P50 MH096890, R01 MH101454]
- National Institute of Neurological Disorders and Stroke (NINDS) grant [R21 NS076958]
- NINDS grant [R01 NS047229]
- National Institute on Aging (NIA) grant [R37 AG017926]
- NIA grant [P50 AG005138]
- Veterans Affairs Merit grant [BX002395]
- Brain Behavior Research Foundation
- American Psychiatric Association-Merck AMP
- Co. Early Academic Career Research Award
- New York Stem Cell Foundation
- Alzheimer's Association grant [IIRG-11-205149]
- Friedman Brain Institute at Icahn School of Medicine at Mount Sinai
- Icahn Institute for Genomics and Multiscale Biology at Icahn School of Medicine at Mount Sinai
- Department of Scientific Computing at the Icahn School of Medicine at Mount Sinai
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.
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