1Am J Psychiatry 2011 Mar 168: 302-16
TitleCopy number variants in schizophrenia: confirmation of five previous findings and new evidence for 3q29 microdeletions and VIPR2 duplications.
AbstractTo evaluate previously reported associations of copy number variants (CNVs) with schizophrenia and to identify additional associations, the authors analyzed CNVs in the Molecular Genetics of schizophrenia study (MGS) and additional available data.
After quality control, MGS data for 3,945 subjects with schizophrenia or schizoaffective disorder and 3,611 screened comparison subjects were available for analysis of rare CNVs (<1% frequency). CNV detection thresholds were chosen that maximized concordance in 151 duplicate assays. Pointwise and genewise analyses were carried out, as well as analyses of previously reported regions. Selected regions were visually inspected and confirmed with quantitative polymerase chain reaction.
In analyses of MGS data combined with other available data sets, odds ratios of 7.5 or greater were observed for previously reported deletions in chromosomes 1q21.1, 15q13.3, and 22q11.21, duplications in 16p11.2, and exon-disrupting deletions in NRXN1. The most consistently supported candidate associations across data sets included a 1.6-Mb deletion in chromosome 3q29 (21 genes, TFRC to BDH1) that was previously described in a mild-moderate mental retardation syndrome, exonic duplications in the gene for vasoactive intestinal peptide receptor 2 (VIPR2), and exonic duplications in C16orf72. The case subjects had a modestly higher genome-wide number of gene-containing deletions (>100 kb and >1 Mb) but not duplications.
The data strongly confirm the association of schizophrenia with 1q21.1, 15q13.3, and 22q11.21 deletions, 16p11.2 duplications, and exonic NRXN1 deletions. These CNVs, as well as 3q29 deletions, are also associated with mental retardation, autism spectrum disorders, and epilepsy. Additional candidate genes and regions, including VIPR2, were identified. Study of the mechanisms underlying these associations should shed light on the pathophysiology of schizophrenia.
SCZ Keywordsschizophrenia
2World J Psychiatry 2013 Sep 3: 57-61
TitleNew findings in the genetics of schizophrenia.
AbstractNew findings in schizophrenia genetics are based on genome-wide association studies (GWAS), research into DNA copy number variations (CNVs), and endophenotypes. More than 70 genes have recently been suspected to be involved in the genetic background of schizophrenia based on the GWAS´s results. They are typically related to neurodevelopment/neuroplasticity, immunology and neuroendocrinology. Nevertheless, for many detected genes their possible relationship to schizophrenia etiopathogenesis is still unknown. The CNVs at genome loci 1q21.1 (candidate gene e.g., PRKAB2), 2p16.3 (candidate gene e.g., NRXN1), 3q29 (candidate genes e.g., BDH1, DLG1, PAK2 or TFRC), 15q11.2 (candidate gene e.g., CYFIP1), 15q13.3 (candidate gene e.g., CHRNA7), 16p13.1 (candidate genes e.g.,NTAN1 or NDE1) and 22q11.2 (candidate genes e.g., COMT, GSTT2 or PRODH) were associated with schizophrenia most frequently. Genetic research of schizophrenia endophenotypes, usually neurophysiological, neuromotoric, neurocognitive, neuroanatomical, neurological or personality-related, will help us to discover the role of relevant genes in the pathogenesis of schizophrenia. It is also necessary to integrate knowledge from other research platforms in schizophrenia, like epigenetics, studies of gene-environment interactions, transcriptomics, proteomics, metabolomics, neuroimaging and psychopathology. A better knowledge of the genetic background of schizophrenia can lead to changes in the treatment, prevention and genetic counselling. It may also reduce stigma in this severe mental disorder.
SCZ Keywordsschizophrenia