HYST: a hybrid set-based test for genome-wide association studies, with application to protein-protein interaction-based association analysis.
paper
Cited
Public
Unavailable
- Authors
- Li, Miao-Xin; Kwan, Johnny S H; Sham, Pak C
- Year
- 2012
- Journal
- American journal of human genetics
- PMID
- 22958900
- DOI
- 10.1016/j.ajhg.2012.08.004
- PMCID
- PMC3511992
The extended Simes' test (known as GATES) and scaled chi-square test were proposed to combine a set of dependent genome-wide association signals at multiple single-nucleotide polymorphisms (SNPs) for assessing the overall significance of association at the gene or pathway levels. The two tests use different strategies to combine association p values and can outperform each other when the number of and linkage disequilibrium between SNPs vary. In this paper, we introduce a hybrid set-based test (HYST) combining the two tests for genome-wide association studies (GWASs). We describe how HYST can be used to evaluate statistical significance for association at the protein-protein interaction (PPI) level in order to increase power for detecting disease-susceptibility genes of moderate effect size. Computer simulations demonstrated that HYST had a reasonable type 1 error rate and was generally more powerful than its parents and other alternative tests to detect a PPI pair where both genes are associated with the disease of interest. We applied the method to three complex disease GWAS data sets in the public domain; the method detected a number of highly connected significant PPI pairs involving multiple confirmed disease-susceptibility genes not found in the SNP- and gene-based association analyses. These results indicate that HYST can be effectively used to examine a collection of predefined SNP sets based on prior biological knowledge for revealing additional disease-predisposing genes of modest effects in GWASs.
No figures extracted from this document.
No chunks β full text not yet ingested.
No entities extracted from this document yet.
No uploaded files.
Not in any collection.
No citations found.
In this knowledge base
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| MARSweb: a fully automated web service for set-based association testing. | Kim T et al. | β | 2025 | β |
| The goldmine of GWAS summary statistics: a systematic review of methods and tools. | Kontou PI et al. | β | 2024 | β |
| Emerging Methods and Resources for BiologicalΒ Interrogation of Neuropsychiatric Polygenic Signal. | Uffelmann E et al. | β | 2021 | β |
| Identifying genetic risk variants associated with brain volumetric phenotypes via K-sample Ball Divergence method. | Hu Y et al. | β | 2021 | β |
| MARS: leveraging allelic heterogeneity to increase power of association testing. | Hormozdiari F et al. | β | 2021 | β |
| A Bayesian hierarchical variable selection prior for pathway-based GWAS using summary statistics. | Yang Y et al. | β | 2020 | β |
| A Bioinformatics Crash Course for Interpreting Genomics Data. | Rotroff DM | β | 2020 | β |
| Explaining the Genetic Causality for Complex Phenotype via Deep Association Kernel Learning. | Bao F et al. | β | 2020 | β |
| Fifteen Years of Gene Set Analysis for High-Throughput Genomic Data: A Review of Statistical Approaches and Future Challenges. | Das S et al. | β | 2020 | β |
| Genetic variants in NECTIN4 encoding an adhesion molecule are associated with continued opioid use. | Fang CP et al. | β | 2020 | β |
| Genome-Wide Meta-Analyses of FTND and TTFC Phenotypes. | Chen J et al. | β | 2020 | β |
| Identification of Novel Genes Associated with Cortical Thickness in Alzheimer's Disease: Systems Biology Approach to Neuroimaging Endophenotype. | Kim BH et al. | β | 2020 | β |
| A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis. | International Multiple Sclerosis Genetics Consortium | β | 2019 | β |
| Efficient region-based test strategy uncovers genetic risk factors for functional outcome in bipolar disorder. | Budde M et al. | β | 2019 | β |
| Genome-wide association analysis of hippocampal volume identifies enrichment of neurogenesis-related pathways. | Horgusluoglu-Moloch E et al. | β | 2019 | β |
| Mucosal Profiling of Pediatric-Onset Colitis and IBD Reveals Common Pathogenics and Therapeutic Pathways. | Huang B et al. | β | 2019 | β |
| Coagulation Factors and the Risk of Ischemic Heart Disease: A Mendelian Randomization Study. | Zhao JV et al. | β | 2018 | β |
| Disconnect Between Genes Associated With Ischemic Heart Disease and Targets of Ischemic Heart Disease Treatments. | Schooling CM et al. | β | 2018 | β |
| Gene-based GWAS analysis for consecutive studies of GEFOS. | Zhu W et al. | β | 2018 | β |
| Genome-wide association meta-analysis of age at first cannabis use. | MinicΔ CC et al. | β | 2018 | β |
| GRK5 Is Associated with the Regulation of Methadone Dosage in Heroin Dependence. | Wang SC et al. | β | 2018 | β |
| Improved Use of Small Reference Panels for Conditional and Joint Analysis with GWAS Summary Statistics. | Deng Y et al. | β | 2018 | β |
| Probabilistic natural mapping of gene-level tests for genome-wide association studies. | Bao F et al. | β | 2018 | β |
| Using Genomic Data to Find Disease-Modifying Loci in Huntington's Disease (HD). | Holmans P et al. | β | 2018 | β |
| A Powerful Gene-Based Test Accommodating Common and Low-Frequency Variants to Detect Both Main Effects and Gene-Gene Interaction Effects in Case-Control Studies. | Chung RH et al. | β | 2017 | β |
| Common variants on 2p16.1, 6p22.1 and 10q24.32 are associated with schizophrenia in Han Chinese population. | Yu H et al. | β | 2017 | β |
| Gene- and pathway-based association tests for multiple traits with GWAS summary statistics. | Kwak IY et al. | β | 2017 | β |
| Improving the detection of pathways in genome-wide association studies by combined effects of SNPs from Linkage Disequilibrium blocks. | Zhao H et al. | β | 2017 | β |
| Missense mutation at CLDN8 associated with a high plasma interferon gamma-inducible protein 10 level in methadone-maintained patients with urine test positive for morphine. | Liu TH et al. | β | 2017 | β |
| Novel genetic loci associated with hippocampal volume. | Hibar DP et al. | β | 2017 | β |
| Oxytocin receptor gene variations predict neural and behavioral response to oxytocin in autism. | Watanabe T et al. | β | 2017 | β |
| Pathway analysis of complex diseases for GWAS, extending to consider rare variants, multi-omics and interactions. | Kao PY et al. | β | 2017 | β |
| Pathways to smoking behaviours: biological insights from the Tobacco and Genetics Consortium meta-analysis. | MinicΓ£ CC et al. | β | 2017 | β |
| Patient complexity and genotype-phenotype correlations in biliary atresia: a cross-sectional analysis. | Cheng G et al. | β | 2017 | β |
| Sharing of Genes and Pathways Across Complex Phenotypes: A Multilevel Genome-Wide Analysis. | Gui H et al. | β | 2017 | β |
| The common variants implicated in microstructural abnormality of first episode and drug-naΓ―ve patients with schizophrenia. | Ren HY et al. | β | 2017 | β |
| Adaptive gene- and pathway-trait association testing with GWAS summary statistics. | Kwak IY et al. | β | 2016 | β |
| A genome-wide association meta-analysis on apolipoprotein A-IV concentrations. | Lamina C et al. | β | 2016 | β |
| A Powerful Procedure for Pathway-based Meta-Analysis Using Summary Statistics Identifies 43 Pathways Associated with Type II Diabetes in European Populations | Zhang H et al. | β | 2016 | β |
| A Powerful Procedure for Pathway-Based Meta-analysis Using Summary Statistics Identifies 43 Pathways Associated with Type II Diabetes in European Populations. | Zhang H et al. | β | 2016 | β |
| Fast set-based association analysis using summary data from GWAS identifies novel gene loci for human complex traits. | Bakshi A et al. | β | 2016 | β |
| Genome-Wide Association and Exome Sequencing Study of Language Disorder in an Isolated Population. | Kornilov SA et al. | β | 2016 | β |
| Genome-wide association meta-analysis in Chinese and European individuals identifies ten new loci associated with systemic lupus erythematosus. | Morris DL et al. | β | 2016 | β |
| Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32 330 subjects from the International Cannabis Consortium. | Stringer S et al. | β | 2016 | β |
| Identification of Common Genetic Variants Influencing Spontaneous Dizygotic Twinning and Female Fertility. | Mbarek H et al. | β | 2016 | β |
| Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium. | van den Berg SM et al. | β | 2016 | β |
| Meta-analysis of lipid-traits in Hispanics identifies novel loci, population-specific effects, and tissue-specific enrichment of eQTLs. | Below JE et al. | β | 2016 | β |
| Meta-analysis of Positive and Negative Symptoms Reveals Schizophrenia Modifier Genes. | Edwards AC et al. | β | 2016 | β |
| Multimarker analysis suggests the involvement of BDNF signaling and microRNA biosynthesis in suicidal behavior. | Pulay AJ et al. | β | 2016 | β |
| Novel genetic loci underlying human intracranial volume identified through genome-wide association. | Adams HH et al. | β | 2016 | β |
| Pathway Analysis Incorporating Protein-Protein Interaction Networks Identified Candidate Pathways for the Seven Common Diseases. | Lin PL et al. | β | 2016 | β |
| Regionally Smoothed Meta-Analysis Methods for GWAS Datasets. | Begum F et al. | β | 2016 | β |
| The statistical properties of gene-set analysis. | de Leeuw CA et al. | β | 2016 | β |
| A cross-species genetic analysis identifies candidate genes for mouse anxiety and human bipolar disorder. | Ashbrook DG et al. | β | 2015 | β |
| A Powerful Pathway-Based Adaptive Test for Genetic Association with Common or Rare Variants. | Pan W et al. | β | 2015 | β |
| Association of chromosome 5q21.3 polymorphisms with the exploratory eye movement dysfunction in schizophrenia. | Ma Y et al. | β | 2015 | β |
| Common genetic variants influence human subcortical brain structures. | Hibar DP et al. | β | 2015 | β |
| Comprehensive gene- and pathway-based analysis of depressive symptoms in older adults. | Nho K et al. | β | 2015 | β |
| Effect of occupational exposures on lung cancer susceptibility: a study of gene-environment interaction analysis. | Malhotra J et al. | β | 2015 | β |
| Evidence for Association of Cell Adhesion Molecules Pathway and NLGN1 Polymorphisms with Schizophrenia in Chinese Han Population. | Zhang Z et al. | β | 2015 | β |
| FASTKD2 is associated with memory and hippocampal structure in older adults. | Ramanan VK et al. | β | 2015 | β |
| Gene-based association analysis identified novel genes associated with bone mineral density. | Mo XB et al. | β | 2015 | β |
| Genome-wide association data suggest ABCB1 and immune-related gene sets may be involved in adult antisocial behavior. | Salvatore JE et al. | β | 2015 | β |
| Genome-wide association study of warfarin maintenance dose in a Brazilian sample. | Parra EJ et al. | β | 2015 | β |
| Genome-wide gene pathway analysis of psychotic illness symptom dimensions based on a new schizophrenia-specific model of the OPCRIT. | Docherty AR et al. | β | 2015 | β |
| Genomic influences on alcohol problems in a population-based sample of young adults. | Edwards AC et al. | β | 2015 | β |
| MAGMA: generalized gene-set analysis of GWAS data. | de Leeuw CA et al. | β | 2015 | β |
| Powerful Tests for Multi-Marker Association Analysis Using Ensemble Learning. | Padhukasahasram B et al. | β | 2015 | β |
| Relative performance of gene- and pathway-level methods as secondary analyses for genome-wide association studies. | Wojcik GL et al. | β | 2015 | β |
| SPS: A Simulation Tool for Calculating Power of Set-Based Genetic Association Tests. | Li J et al. | β | 2015 | β |
| SWI/SNF chromatin remodeling regulates alcohol response behaviors in Caenorhabditis elegans and is associated with alcohol dependence in humans. | Mathies LD et al. | β | 2015 | β |
| A hypothesis-driven pathway analysis reveals myelin-related pathways that contribute to the risk of schizophrenia and bipolar disorder. | Yu H et al. | β | 2014 | β |
| Functional and genomic context in pathway analysis of GWAS data. | Mooney MA et al. | β | 2014 | β |
| Genome-wide association studies of suicidal behaviors: a review. | Sokolowski M et al. | β | 2014 | β |
| Meta-analysis of genome-wide association studies identifies two loci associated with circulating osteoprotegerin levels. | Kwan JS et al. | β | 2014 | β |
| VarWalker: personalized mutation network analysis of putative cancer genes from next-generation sequencing data. | Jia P et al. | β | 2014 | β |
| Gene-based testing of interactions in association studies of quantitative traits. | Ma L et al. | β | 2013 | β |