ArticleBMC genetics2015
Relative performance of gene- and pathway-level methods as secondary analyses for genome-wide association studies.
Article in BMC genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 2 of them syntheses that pooled it.
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Who cites it
22 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Multivariate analysis of genome-wide data to identify potential pleiotropic genes for five major psychiatric disorders using MetaCCA.Journal of affective disorders · 2019Pooled it
- Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia.Molecular autism · 2017Pooled it
- Multi-omics cannot replace sample size in genome-wide association studies.Genes, brain, and behavior · 2023Article
- Evaluating 17 methods incorporating biological function with GWAS summary statistics to accelerate discovery demonstrates a tradeoff between high sensitivity and high positive predictive value.Communications biology · 2023Article
- Impact of NLRP3 gene polymorphisms (rs10754558 and rs10733113) on HPV infection and cervical cancer in southern Chinese population.Infectious agents and cancer · 2023Article
- Mapping gene and gene pathways associated with coronary artery disease: a CARDIoGRAM exome and multi-ancestry UK biobank analysis.Scientific reports · 2021Article
- Detecting Shared Genetic Architecture Among Multiple Phenotypes by Hierarchical Clustering of Gene-Level Association Statistics.Genetics · 2020Article
- Germline Features Associated with Immune Infiltration in Solid Tumors.Cell reports · 2020Article
- Identification of 67 Pleiotropic Genes Associated With Seven Autoimmune/Autoinflammatory Diseases Using Multivariate Statistical Analysis.Frontiers in immunology · 2020Article
- Association Mapping Based on a Common-Garden Migration Experiment Reveals Candidate Genes for Migration Tendency in Brown Trout.G3 (Bethesda, Md.) · 2019Article
- Maternal cardiovascular-related single nucleotide polymorphisms, genes, and pathways associated with early-onset preeclampsia.PloS one · 2019Article
- Shared activity patterns arising at genetic susceptibility loci reveal underlying genomic and cellular architecture of human disease.PLoS computational biology · 2018Article
- Article
- Gene-level association analysis of systemic sclerosis: A comparison of African-Americans and White populations.PloS one · 2018Article
- Analysis of the Influence of microRNAs in Lithium Response in Bipolar Disorder.Frontiers in psychiatry · 2018Article
- Hierarchical investigation of genetic influences on response inhibition in healthy young adults.Experimental and clinical psychopharmacology · 2017Article
- Novel Gene and Network Associations Found for Acute Lymphoblastic Leukemia Using Case-Control and Family-Based Studies in Multiethnic Populations.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2017Article
- Bayesian genome- and epigenome-wide association studies with gene level dependence.Biometrics · 2017Article
- Gene-wide Association Study Reveals RNF122 Ubiquitin Ligase as a Novel Susceptibility Gene for Attention Deficit Hyperactivity Disorder.Scientific reports · 2017Article
- PR Interval Associated Genes, Atrial Remodeling and Rhythm Outcome of Catheter Ablation of Atrial Fibrillation-A Gene-Based Analysis of GWAS Data.Frontiers in genetics · 2017Article
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Authors and funding
3 authors.
Funding
Abstract
backgroundDespite the success of genome-wide association studies (GWAS), there still remains "missing heritability" for many traits. One contributing factor may be the result of examining one marker at a time as opposed to a group of markers that are biologically meaningful in aggregate. To address this problem, a variety of gene- and pathway-level methods have been developed to identify putative biologically relevant associations. A simulation was conducted to systematically assess the performance of these methods. Using genetic data from 4,500 individuals in the Wellcome Trust Case Control Consortium (WTCCC), case-control status was simulated based on an additive polygenic model. We evaluated gene-level methods based on their sensitivity, specificity, and proportion of false positives. Pathway-level methods were evaluated on the relationship between proportion of causal genes within the pathway and the strength of association.
resultsThe gene-level methods had low sensitivity (20-63%), high specificity (89-100%), and low proportion of false positives (0.1-6%). The gene-level program VEGAS using only the top 10% of associated single nucleotide polymorphisms (SNPs) within the gene had the highest sensitivity (28.6%) with less than 1% false positives. The performance of the pathway-level methods depended on their reliance upon asymptotic distributions or if significance was estimated in a competitive manner. The pathway-level programs GenGen, GSA-SNP and MAGENTA had the best performance while accounting for potential confounders.
conclusionsNovel genes and pathways can be identified using the gene and pathway-level methods. These methods may provide valuable insight into the "missing heritability" of traits and provide biological interpretations to GWAS findings.
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