ArticleSchizophrenia bulletin2015
Systematic Integration of Brain eQTL and GWAS Identifies ZNF323 as a Novel Schizophrenia Risk Gene and Suggests Recent Positive Selection Based on Compensatory Advantage on Pulmonary Function.
Article in Schizophrenia bulletin, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Genome-wide association study followed by trans-ancestry meta-analysis identify 17 new risk loci for schizophrenia.BMC medicine · 2021Pooled it
- Effects of Schizophrenia, Bipolar Disorder, and Depression on Cardiopulmonary and Abdominal Organ Structure.Biological psychiatry global open science · 2026Article
- Expression patterns of risk genes associated with three evolutionarily relevant syndromes in rhesus macaque and human brains.Translational psychiatry · 2026Article
- Deciphering cell type-specific causal genetic effects on brain imaging-derived phenotypes and disorders with single-cell Mendelian randomization.PLoS computational biology · 2026Article
- Genetic and functional insights into long noncoding RNAs in schizophrenia.Molecular psychiatry · 2026Article
- A review of post-GWAS studies in schizophrenia.Translational psychiatry · 2025Review
- Differential gene expression study in whole blood identifies candidate genes for psychosis in African American individuals.Schizophrenia research · 2025Article
- Autism and schizophrenia spectrum disorder: phenomenological qualitative study of patients' experience.Frontiers in psychiatry · 2025Article
- Analyses of the autism-associated neuroligin-3 R451C mutation in human neurons reveal a gain-of-function synaptic mechanism.Molecular psychiatry · 2024Article
- Recent natural selection conferred protection against schizophrenia by non-antagonistic pleiotropy.Scientific reports · 2023Article
- Whole-genome sequencing analysis of suicide deaths integrating brain-regulatory eQTLs data to identify risk loci and genes.Molecular psychiatry · 2023Article
- Shared genetics and causal relationships between major depressive disorder and COVID-19 related traits: a large-scale genome-wide cross-trait meta-analysis.Frontiers in psychiatry · 2023Article
- Single molecule in situ hybridization reveals distinct localizations of schizophrenia risk-related transcripts SNX19 and AS3MT in human brain.Molecular psychiatry · 2021Article
- Epigenome-wide association study on asthma and chronic obstructive pulmonary disease overlap reveals aberrant DNA methylations related to clinical phenotypes.Scientific reports · 2021Article
- A transcription-centric model of SNP-age interaction.PLoS genetics · 2021Article
- In Silico Analysis of Possible Interaction between Host Genomic Transcription Factors (TFs) and Zika Virus (ZikaSPH2015) Strain with Combinatorial Gene Regulation; Virus Versus Host-The Game Reloaded.Pathogens (Basel, Switzerland) · 2021Article
- Comprehensive DNA Methylation Analysis of Human Neuroblastoma Cells Treated With Haloperidol and Risperidone.Frontiers in molecular neuroscience · 2021Article
- Expression quantitative trait loci-derived scores and white matter microstructure in UK Biobank: a novel approach to integrating genetics and neuroimaging.Translational psychiatry · 2020Article
- CFrontiers in neurology · 2020Review
- Integrative analyses of major histocompatibility complex loci in the genome-wide association studies of major depressive disorder.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2019Article
Corrections and comments
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Authors and funding
22 authors at 12 institutions in 6 countries.
Funding
Abstract
Genome-wide association studies have identified multiple risk variants and loci that show robust association with schizophrenia. Nevertheless, it remains unclear how these variants confer risk to schizophrenia. In addition, the driving force that maintains the schizophrenia risk variants in human gene pool is poorly understood. To investigate whether expression-associated genetic variants contribute to schizophrenia susceptibility, we systematically integrated brain expression quantitative trait loci and genome-wide association data of schizophrenia using Sherlock, a Bayesian statistical framework. Our analyses identified ZNF323 as a schizophrenia risk gene (P = 2.22×10(-6)). Subsequent analyses confirmed the association of the ZNF323 and its expression-associated single nucleotide polymorphism rs1150711 in independent samples (gene-expression: P = 1.40×10(-6); single-marker meta-analysis in the combined discovery and replication sample comprising 44123 individuals: P = 6.85×10(-10)). We found that the ZNF323 was significantly downregulated in hippocampus and frontal cortex of schizophrenia patients (P = .0038 and P = .0233, respectively). Evidence for pleiotropic effects was detected (association of rs1150711 with lung function and gene expression of ZNF323 in lung: P = 6.62×10(-5) and P = 9.00×10(-5), respectively) with the risk allele (T allele) for schizophrenia acting as protective allele for lung function. Subsequent population genetics analyses suggest that the risk allele (T) of rs1150711 might have undergone recent positive selection in human population. Our findings suggest that the ZNF323 is a schizophrenia susceptibility gene whose expression may influence schizophrenia risk. Our study also illustrates a possible mechanism for maintaining schizophrenia risk variants in the human gene pool.
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