New discoveries in schizophrenia genetics reveal neurobiological pathways: A review of recent findings.
Schizophrenia research has undergone a recent transformation. By leveraging large sample sizes, genome-wide association studies of common genetic variants have approximately tripled the number of candidate genetic loci. Rare variant studies have identified copy number variants that are schizophrenia risk loci. Among these, the 3q29 microdeletion is now known to be the single largest schizophrenia risk factor. Next-generation sequencing studies are increasingly used for rare variant association testing, and have already facilitated identification of large effect alleles. Collectively, recent findings implicate voltage-gated calcium channel and cytoskeletal pathways in the pathogenesis of schizophrenia. Taken together, these results suggest the possibility of imminent breakthroughs in the molecular understanding of schizophrenia.
Graduate Program in Genetics and Molecular Biology, Emory University, Atlanta GA, USA.
Alex V
AV
Kotlar
Graduate Program in Genetics and Molecular Biology, Emory University, Atlanta GA, USA.
Kristina B
KB
Mercer
Department of Human Genetics, Emory University School of Medicine, Atlanta GA, USA; Department of Pediatrics, Emory University School of Medicine, Atlanta GA, USA.
Michael E
ME
Zwick
Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta GA, USA; Department of Human Genetics, Emory University School of Medicine, Atlanta GA, USA. Electronic address: jmulle@emory.edu.
Jennifer G
JG
Mulle
D002869:Chromosome Aberrations; D056915:DNA Copy Number Variations; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D023281:Genomics / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D001523:Mental Disorders / Q000235:genetics / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction
Copy number variation; GWAS; Psychiatric genetics; Schizophrenia genetics