Meta-analysis of Positive and Negative Symptoms Reveals Schizophrenia Modifier Genes.
- Authors
- Edwards, Alexis C; Bigdeli, Tim B; Docherty, Anna R; Bacanu, Silviu; Lee, Donghyung; de Candia, Teresa R; Moscati, Arden; Thiselton, Dawn L; Maher, Brion S; Wormley, Brandon K; Molecular Genetics of Schizophrenia Collaboration (MGS); Walsh, Dermot; O'Neill, Francis A; Kendler, Kenneth S; Riley, Brien P; Fanous, Ayman H
- Year
- 2016
- Journal
- Schizophrenia bulletin
- PMID
- 26316594
- DOI
- 10.1093/schbul/sbv119
- PMCID
- PMC4753595
BACKGROUND: Evidence suggests that genetic factors may influence both schizophrenia (Scz) and its clinical presentation. In recent years, genome-wide association studies (GWAS) have demonstrated considerable success in identifying risk loci. Detection of "modifier loci" has the potential to further elucidate underlying disease processes. METHODS: We performed GWAS of empirically derived positive and negative symptom scales in Irish cases from multiply affected pedigrees and a larger, independent case-control sample, subsequently combining these into a large Irish meta-analysis. In addition to single-SNP associations, we considered gene-based and pathway analyses to better capture convergent genetic effects, and to facilitate biological interpretation of these findings. Replication and testing of aggregate genetic effects was conducted using an independent European-American sample. RESULTS: Though no single marker met the genome-wide significance threshold, genes and ontologies/pathways were significantly associated with negative and positive symptoms; notably, NKAIN2 and NRG1, respectively. We observed limited overlap in ontologies/pathways associated with different symptom profiles, with immune-related categories over-represented for negative symptoms, and addiction-related categories for positive symptoms. Replication analyses suggested that genes associated with clinical presentation are generalizable to non-Irish samples. CONCLUSIONS: These findings strongly support the hypothesis that modifier loci contribute to the etiology of distinct Scz symptom profiles. The finding that previously implicated "risk loci" actually influence particular symptom dimensions has the potential to better delineate the roles of these genes in Scz etiology. Furthermore, the over-representation of distinct gene ontologies/pathways across symptom profiles suggests that the clinical heterogeneity of Scz is due in part to complex and diverse genetic factors.
No figures extracted from this document.
No chunks β full text not yet ingested.
No entities extracted from this document yet.
No uploaded files.
No citations found.
In this knowledge base
| Title | Year | PMID |
|---|---|---|
| Post-GWAS in Psychiatric Genetics: A Developmental Perspective on the "Other" Next Steps. | 2018 | 29227573 |
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Beyond vertebrates: <i>Drosophila melanogaster</i> as a model to study negative symptoms of schizophrenia. | Elgueta-Reyes M et al. | β | 2025 | β |
| Rare Copy Number Variation in Schizophrenia and Implications for Treatment. | Docherty AR | β | 2023 | β |
| The Effect of Clozapine and Novel Glutamate Modulator JNJ-46356479 on Nitrosative Stress in a Postnatal Murine Ketamine Model of Schizophrenia. | Treder N et al. | β | 2023 | β |
| Association of g-quadruplex variants with schizophrenia symptoms. | Bhattacharyya U et al. | β | 2022 | β |
| A study of the association between polymorphisms in the genes for interleukins IL-6 and IL-10 and negative symptoms subdomains in schizophrenia. | Golimbet V et al. | β | 2022 | β |
| Perceptual inference, accuracy, and precision in temporal reproduction in schizophrenia. | Ueda N et al. | β | 2022 | β |
| Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders. | Blokland GAM et al. | β | 2022 | β |
| A Bioecosystem Theory of Negative Symptoms in Schizophrenia. | Strauss GP | β | 2021 | β |
| Developments in Biological Mechanisms and Treatments for Negative Symptoms and Cognitive Dysfunction of Schizophrenia. | Wu Q et al. | β | 2021 | β |
| Evidence of an interaction between <i>FXR1</i> and <i>GSK3Ξ²</i> polymorphisms on levels of Negative Symptoms of Schizophrenia and their response to antipsychotics. | Rampino A et al. | β | 2021 | β |
| Genome-wide association study identified INSC gene associated with Trail Making Test Part A and Alzheimer's disease related cognitive phenotypes. | Wang K et al. | β | 2021 | β |
| Large-scale evaluation of the Positive and Negative Syndrome Scale (PANSS) symptom architecture in schizophrenia. | Lim K et al. | β | 2021 | β |
| The continuity of effect of schizophrenia polygenic risk score and patterns of cannabis use on transdiagnostic symptom dimensions at first-episode psychosis: findings from the EU-GEI study. | Quattrone D et al. | β | 2021 | β |
| Associations between schizophrenia polygenic risk and apathy in schizophrenia spectrum disorders and healthy controls. | Lyngstad SH et al. | β | 2020 | β |
| Current challenges and possible future developments in personalized psychiatry with an emphasis on psychotic disorders. | Levchenko A et al. | β | 2020 | β |
| Exploring the neuropsychiatric spectrum using high-content functional analysis of single-cell signaling networks. | Lago SG et al. | β | 2020 | β |
| Polygenic Risk Scores for Subtyping of Schizophrenia. | Chen J et al. | β | 2020 | β |
| Schizophrenia, Not a Psychotic Disorder: Bleuler Revisited. | Loch AA | β | 2019 | β |
| Schizophrenia polygenic risk score and cannabis use modify psychosis expression in first episode psychosis patients and population controls | Quattrone D et al. | β | 2019 | β |
| Association between COMT gene polymorphisms, clinical symptoms, and cognitive functions in Han Chinese patients with schizophrenia. | Sun Z et al. | β | 2018 | β |
| Epigenetic meta-analysis across three civilian cohorts identifies NRG1 and HGS as blood-based biomarkers for post-traumatic stress disorder. | Uddin M et al. | β | 2018 | β |
| Post-GWAS in Psychiatric Genetics: A Developmental Perspective on the "Other" Next Steps. | Dick DM et al. | β | 2018 | β |
| Advancing psychiatric genetics through dissecting heterogeneity. | Hodgson K et al. | β | 2017 | β |
| Association of transcription factor 4 (TCF4) gene mRNA level with schizophrenia, its psychopathology, intelligence and cognitive impairments. | Alizadeh F et al. | β | 2017 | β |
| Genetic loci associated with an earlier age at onset in multiplex schizophrenia. | Woolston AL et al. | β | 2017 | β |
| Schizophrenia genetics comes to translation. | Domenici E | β | 2017 | β |
| Consensus paper of the WFSBP Task Force on Biological Markers: Criteria for biomarkers and endophenotypes of schizophrenia part II: Cognition, neuroimaging and genetics. | Schmitt A et al. | β | 2016 | β |
| Cross-Disorder Psychiatric Genomics. | Docherty AR et al. | β | 2016 | β |
| From Linkage Studies to Epigenetics: What We Know and What We Need to Know in the Neurobiology of Schizophrenia. | Cariaga-Martinez A et al. | β | 2016 | β |
| Parsing psychosis subtypes through investigations of rare genetic variants. | Bergen SE | β | 2016 | β |
| The role of the ITIH3 rs2535629 variant in antipsychotic response. | Brandl EJ et al. | β | 2016 | β |