ArticleTranslational psychiatry2015
Analysis of exome sequence in 604 trios for recessive genotypes in schizophrenia.
Article in Translational psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 41 citations in OpenAlex.
- Identification of hub genes involved in early-onset schizophrenia: from genetic susceptibility to predicted regulated gene expression.Molecular psychiatry · 2026Article
- Identification of Hub Genes Involved in Early-onset Schizophrenia: From Genetic Susceptibility to Predicted Regulated Gene Expression.Research square · 2025Article
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- Whole Exome-Trio Analysis Reveals Rare Variants Associated with Congenital Pouch Colon.Children (Basel, Switzerland) · 2023Article
- Mutation screening of SPTLC1 and SPTLC2 in amyotrophic lateral sclerosis.Human genomics · 2023Article
- Lack of association of TP73 rare variants with amyotrophic lateral sclerosis in a Chinese cohort.Human genomics · 2022Article
- SCN2A channelopathies in the autism spectrum of neuropsychiatric disorders: a role for pluripotent stem cells?Molecular autism · 2020Review
- Assessment of Potential Clinical Role for Exome Sequencing in Schizophrenia.Schizophrenia bulletin · 2020Article
- Genomic profiling of 553 uncharacterized neurodevelopment patients reveals a high proportion of recessive pathogenic variant carriers in an outbred population.Scientific reports · 2020Article
- Novel genetic susceptibility loci identified by family based whole exome sequencing in Han Chinese schizophrenia patients.Translational psychiatry · 2020Article
- Targeted Sequencing of 10,198 Samples Confirms Abnormalities in Neuronal Activity and Implicates Voltage-Gated Sodium Channels in Schizophrenia Pathogenesis.Biological psychiatry · 2019Article
- Rare Variants in Tissue Inhibitor of Metalloproteinase 2 as a Risk Factor for Schizophrenia: Evidence From Familial and Cohort Analysis.Schizophrenia bulletin · 2019Article
- Schizophrenia and Hereditary Polyneuropathy:Frontiers in psychiatry · 2019Article
- Rare compound heterozygous missenseNeuropsychiatric disease and treatment · 2019Article
- A novel homozygous mutation in GAD1 gene described in a schizophrenic patient impairs activity and dimerization of GAD67 enzyme.Scientific reports · 2018Article
- Rare variant analysis in multiply affected families, association studies and functional analysis suggest a role for the ITGΒ4 gene in schizophrenia and bipolar disorder.Schizophrenia research · 2018Article
- Recent Advances in the Genetics of Schizophrenia.Molecular neuropsychiatry · 2018Review
- Weighted Burden Analysis of Exome-Sequenced Case-Control Sample Implicates Synaptic Genes in Schizophrenia Aetiology.Behavior genetics · 2018Article
- An examination of multiple classes of rare variants in extended families with bipolar disorder.Translational psychiatry · 2018Article
- Identification of rare nonsynonymous variants in SYNE1/CPG2 in bipolar affective disorder.Psychiatric genetics · 2017Article
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Authors and funding
38 authors at 11 institutions in 5 countries.
Funding
Abstract
Genetic associations involving both rare and common alleles have been reported for schizophrenia but there have been no systematic scans for rare recessive genotypes using fully phased trio data. Here, we use exome sequencing in 604 schizophrenia proband-parent trios to investigate the role of recessive (homozygous or compound heterozygous) nonsynonymous genotypes in the disorder. The burden of recessive genotypes was not significantly increased in probands at either a genome-wide level or in any individual gene after adjustment for multiple testing. At a system level, probands had an excess of nonsynonymous compound heterozygous genotypes (minor allele frequency, MAF ⩽ 1%) in voltage-gated sodium channels (VGSCs; eight in probands and none in parents, P = 1.5 × 10(-)(4)). Previous findings of multiple de novo loss-of-function mutations in this gene family, particularly SCN2A, in autism and intellectual disability provide biological and genetic plausibility for this finding. Pointing further to the involvement of VGSCs in schizophrenia, we found that these genes were enriched for nonsynonymous mutations (MAF ⩽ 0.1%) in cases genotyped using an exome array, (5585 schizophrenia cases and 8103 controls), and that in the trios data, synaptic proteins interacting with VGSCs were also enriched for both compound heterozygosity (P = 0.018) and de novo mutations (P = 0.04). However, we were unable to replicate the specific association with compound heterozygosity at VGSCs in an independent sample of Taiwanese schizophrenia trios (N = 614). We conclude that recessive genotypes do not appear to make a substantial contribution to schizophrenia at a genome-wide level. Although multiple lines of evidence, including several from this study, suggest that rare mutations in VGSCs contribute to the disorder, in the absence of replication of the original findings regarding compound heterozygosity, this conclusion requires evaluation in a larger sample of trios.
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