ArticleTranslational psychiatry2012
Epistasis network centrality analysis yields pathway replication across two GWAS cohorts for bipolar disorder.
Article in Translational psychiatry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 65 citations in OpenAlex.
- BridGE: a pathway-based analysis tool for detecting genetic interactions from GWAS.Nature protocols · 2024Review
- A genome-wide association study of tinnitus reveals shared genetic links to neuropsychiatric disorders.Scientific reports · 2022Article
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- Cancer Risk Score Prediction Based on a Single-Nucleotide Polymorphism Network.Healthcare informatics research · 2022Article
- A systematic analysis of gene-gene interaction in multiple sclerosis.BMC medical genomics · 2022Article
- Integration of functional genomics data to uncover cell type-specific pathways affected in Parkinson's disease.Biochemical Society transactions · 2021Review
- PIP-SNP: a pipeline for processing SNP data featured as linkage disequilibrium bin mapping, genotype imputing and marker synthesizing.NAR genomics and bioinformatics · 2021Article
- Teneurins: Role in Cancer and Potential Role as Diagnostic Biomarkers and Targets for Therapy.International journal of molecular sciences · 2021Review
- Sleep and Memory Consolidation Dysfunction in Psychiatric Disorders: Evidence for the Involvement of Extracellular Matrix Molecules.Frontiers in neuroscience · 2021Review
- The genetics of bipolar disorder.Molecular psychiatry · 2020Review
- GPU empowered pipelines for calculating genome-wide kinship matrices with ultra-high dimensional genetic variants and facilitating 1D and 2D GWAS.NAR genomics and bioinformatics · 2020Article
- Discovering genetic interactions bridging pathways in genome-wide association studies.Nature communications · 2019Article
- EpistasisRank and EpistasisKatz: interaction network centrality methods that integrate prior knowledge networks.Bioinformatics (Oxford, England) · 2019Article
- 2D association and integrative omics analysis in rice provides systems biology view in trait analysis.Communications biology · 2018Article
- Stability and change in etiological factors for alcohol use disorder and major depression.Journal of abnormal psychology · 2017Article
- Decreased Numbers of Somatostatin-Expressing Neurons in the Amygdala of Subjects With Bipolar Disorder or Schizophrenia: Relationship to Circadian Rhythms.Biological psychiatry · 2017Article
- A novel relationship for schizophrenia, bipolar and major depressive disorder Part 5: a hint from chromosome 5 high density association screen.American journal of translational research · 2017Article
- Ankyrin G expression is associated with androgen receptor stability, invasiveness, and lethal outcome in prostate cancer patients.Journal of molecular medicine (Berlin, Germany) · 2016Article
- Common variants on 17q25 and gene-gene interactions conferring risk of schizophrenia in Han Chinese population and regulating gene expressions in human brain.Molecular psychiatry · 2016Article
- Genetic variants in Alzheimer disease - molecular and brain network approaches.Nature reviews. Neurology · 2016Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Most pathway and gene-set enrichment methods prioritize genes by their main effect and do not account for variation due to interactions in the pathway. A portion of the presumed missing heritability in genome-wide association studies (GWAS) may be accounted for through gene-gene interactions and additive genetic variability. In this study, we prioritize genes for pathway enrichment in GWAS of bipolar disorder (BD) by aggregating gene-gene interaction information with main effect associations through a machine learning (evaporative cooling) feature selection and epistasis network centrality analysis. We validate this approach in a two-stage (discovery/replication) pathway analysis of GWAS of BD. The discovery cohort comes from the Wellcome Trust Case Control Consortium (WTCCC) GWAS of BD, and the replication cohort comes from the National Institute of Mental Health (NIMH) GWAS of BD in European Ancestry individuals. Epistasis network centrality yields replicated enrichment of Cadherin signaling pathway, whose genes have been hypothesized to have an important role in BD pathophysiology but have not demonstrated enrichment in previous analysis. Other enriched pathways include Wnt signaling, circadian rhythm pathway, axon guidance and neuroactive ligand-receptor interaction. In addition to pathway enrichment, the collective network approach elevates the importance of ANK3, DGKH and ODZ4 for BD susceptibility in the WTCCC GWAS, despite their weak single-locus effect in the data. These results provide evidence that numerous small interactions among common alleles may contribute to the diathesis for BD and demonstrate the importance of including information from the network of gene-gene interactions as well as main effects when prioritizing genes for pathway analysis.
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