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.
The I-II loop of the Ca2+ channel alpha1 subunit contains an endoplasmic reticulum retention signal antagonized by the beta subunit
Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder
Developmental regulation and individual differences of neuronal H3K4me3 epigenomes in the prefrontal cortex
Schizophrenia susceptibility alleles are enriched for alleles that affect gene expression in adult human brain
The CACNA1C and ANK3 risk alleles impact on affective personality traits and startle reactivity but not on cognition or gating in healthy males
Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4.
Genetics of gene expression in primary immune cells identifies cell type-specific master regulators and roles of HLA alleles
The impact of CACNA1C allelic variation on effective connectivity during emotional processing in bipolar disorder
Effects of the CACNA1C risk allele on neurocognition in patients with schizophrenia and healthy individuals
Association of rs1006737 in CACNA1C with alterations in prefrontal activation and fronto-hippocampal connectivity
A rare mutation of CACNA1C in a patient with bipolar disorder, and decreased gene expression associated with a bipolar-associated common SNP of CACNA1C in brain
Genome-wide DNA methylation profiling in the superior temporal gyrus reveals epigenetic signatures associated with Alzheimer's disease
New statistical approaches exploit the polygenic architecture of schizophrenia--implications for the underlying neurobiology
Practical Guidelines for High-Resolution Epigenomic Profiling of Nucleosomal Histones in Postmortem Human Brain Tissue
Epigenomic mapping and effect sizes of noncoding variants associated with psychotropic drug response
A glutamatergic network mediates lithium response in bipolar disorder as defined by epigenome pathway analysis
Concise Review: Progress and Challenges in Using Human Stem Cells for Biological and Therapeutics Discovery: Neuropsychiatric Disorders
Genome-wide significant schizophrenia risk variation on chromosome 10q24 is associated with altered cis-regulation of BORCS7, AS3MT, and NT5C2 in the human brain.
Targeted resequencing of regulatory regions at schizophrenia risk loci: Role of rare functional variants at chromatin repressive states
Sex-dependent modulation of age-related cognitive decline by the L-type calcium channel gene Cacna1c (Cav 1.2)
Expression quantitative trait loci (eQTLs) in microRNA genes are enriched for schizophrenia and bipolar disorder association signals
The Relationship of Common Risk Variants and Polygenic Risk for Schizophrenia to Sensorimotor Gating
Genetic Differences in the Immediate Transcriptome Response to Stress Predict Risk-Related Brain Function and Psychiatric Disorders
Resequencing and association analysis of coding regions at twenty candidate genes suggest a role for rare risk variation at AKAP9 and protective variation at NRXN1 in schizophrenia susceptibility
Beyond the usual suspects: a multidimensional genetic exploration of infant attachment disorganization and security
Schizophrenia risk variants affecting microRNA function and site-specific regulation of NT5C2 by miR-206
L-type Ca2+ channels in mood, cognition and addiction: integrating human and rodent studies with a focus on behavioural endophenotypes
Consensus paper of the WFSBP Task Force on Biological Markers: Criteria for biomarkers and endophenotypes of schizophrenia, part III: Molecular mechanisms
Genomic and network patterns of schizophrenia genetic variation in human evolutionary accelerated regions
Rescue of impaired sociability and anxiety-like behavior in adult cacna1c-deficient mice by pharmacologically targeting eIF2α
Genetic analysis of schizophrenia and bipolar disorder reveals polygenicity but also suggests new directions for molecular interrogation
Assessment of de novo copy-number variations in Italian patients with schizophrenia: Detection of putative mutations involving regulatory enhancer elements
Novel Bioinformatics Approach Identifies Transcriptional Profiles of Lineage-Specific Transposable Elements at Distinct Loci in the Human Dorsolateral Prefrontal Cortex
Identification of expression quantitative trait loci associated with schizophrenia and affective disorders in normal brain tissue
Sex-dependent effects of Cacna1c haploinsufficiency on juvenile social play behavior and pro-social 50-kHz ultrasonic communication in rats
An integrative functional genomics framework for effective identification of novel regulatory variants in genome-phenome studies
CREs: Gene & Cell Therapy
Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.
Bipolar disorder is characterized by manic and/or depressive episodes and associated with uncommon shifts in mood, activity levels, and energy. Discover the latest research this illness here.