ArticleGenetic epidemiology2015
iGWAS: Integrative Genome-Wide Association Studies of Genetic and Genomic Data for Disease Susceptibility Using Mediation Analysis.
Article in Genetic epidemiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
28 citing papers in PubMed, 44 citations in OpenAlex.
- Gene network and biological pathways associated with susceptibility to differentiated thyroid carcinoma.Scientific reports · 2021Trial
- Causal Mediation Analysis for Integrating Exposure, Genomic, and Phenotype Data.Annual review of statistics and its application · 2025Article
- Application of Mendelian randomization to explore the genetic association between drinking habits of different beverages and sleep disorder.Archives of medical science : AMS · 2025Article
- A mediation analysis framework based on variance component to remove genetic confounding effect.Journal of human genetics · 2024Article
- Methods for large-scale single mediator hypothesis testing: Possible choices and comparisons.Genetic epidemiology · 2023Review
- Integrating multi-omics summary data using a Mendelian randomization framework.Briefings in bioinformatics · 2022Article
- Secondary analyses for genome-wide association studies using expression quantitative trait loci.Genetic epidemiology · 2022Article
- Generalized multi-SNP mediation intersection-union test.Biometrics · 2022Article
- Varying Coefficient Mediation Model and Application to Analysis of Behavioral Economics Data.Journal of business & economic statistics : a publication of the American Statistical Association · 2022Article
- Integrating genome-wide association and transcriptome prediction model identifies novel target genes for osteoporosis.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2021Article
- Discover novel disease-associated genes based on regulatory networks of long-range chromatin interactions.Methods (San Diego, Calif.) · 2021Article
- Estimation and inference for the indirect effect in high-dimensional linear mediation models.Biometrika · 2020Article
- MCC-SP: a powerful integration method for identification of causal pathways from genetic variants to complex disease.BMC genetics · 2020Article
- The GeneG3 (Bethesda, Md.) · 2020Article
- A latent unknown clustering integrating multi-omics data (LUCID) with phenotypic traits.Bioinformatics (Oxford, England) · 2020Article
- An Information-Based Approach for Mediation Analysis on High-Dimensional Metagenomic Data.Frontiers in genetics · 2020Article
- iFunMed: Integrative functional mediation analysis of GWAS and eQTL studies.Genetic epidemiology · 2019Article
- Identifying and exploiting gene-pathway interactions from RNA-seq data for binary phenotype.BMC genetics · 2019Article
- Testing Mediation Effects in High-Dimensional Epigenetic Studies.Frontiers in genetics · 2019Article
- Learning Causal Biological Networks With the Principle of Mendelian Randomization.Frontiers in genetics · 2019Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Genome-wide association studies (GWAS) have been a standard practice in identifying single nucleotide polymorphisms (SNPs) for disease susceptibility. We propose a new approach, termed integrative GWAS (iGWAS) that exploits the information of gene expressions to investigate the mechanisms of the association of SNPs with a disease phenotype, and to incorporate the family-based design for genetic association studies. Specifically, the relations among SNPs, gene expression, and disease are modeled within the mediation analysis framework, which allows us to disentangle the genetic effect on a disease phenotype into two parts: an effect mediated through a gene expression (mediation effect, ME) and an effect through other biological mechanisms or environment-mediated mechanisms (alternative effect, AE). We develop omnibus tests for the ME and AE that are robust to underlying true disease models. Numerical studies show that the iGWAS approach is able to facilitate discovering genetic association mechanisms, and outperforms the SNP-only method for testing genetic associations. We conduct a family-based iGWAS of childhood asthma that integrates genetic and genomic data. The iGWAS approach identifies six novel susceptibility genes (MANEA, MRPL53, LYCAT, ST8SIA4, NDFIP1, and PTCH1) using the omnibus test with false discovery rate less than 1%, whereas no gene using SNP-only analyses survives with the same cut-off. The iGWAS analyses further characterize that genetic effects of these genes are mostly mediated through their gene expressions. In summary, the iGWAS approach provides a new analytic framework to investigate the mechanism of genetic etiology, and identifies novel susceptibility genes of childhood asthma that were biologically meaningful.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.