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ExPheWas: a platform for cis-Mendelian randomization and gene-based association scans.

ABSTRACT: Establishing the relationship between protein-coding genes and phenotypes has the potential to inform on the molecular etiology of diseases. Here, we describe ExPheWas (exphewas.ca), a gene-based phenome-wide association study browser and platform that enables the conduct of gene-based Mendelian randomization. The ExPheWas data repository includes sex-stratified and sex-combined gene-based association results from 26 616 genes with 1746 phenotypes measured in up to 413 133 individuals from the UK Biobank. Interactive visualizations are provided through a browser to facilitate data exploration supported by false discovery rate control, and it includes tools for enrichment analysis. The interactive Mendelian randomization module in ExPheWas allows the estimation of causal effects of a genetically predicted exposure on an outcome by using genetic variation in a single gene as the instrumental variable.

SUBMITTER: Legault MA

PROVIDER: S-EPMC9252780 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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ExPheWas: a platform for cis-Mendelian randomization and gene-based association scans.

Legault Marc-André MA Perreault Louis-Philippe Lemieux LL Tardif Jean-Claude JC Dubé Marie-Pierre MP

Nucleic acids research 20220701 W1

Establishing the relationship between protein-coding genes and phenotypes has the potential to inform on the molecular etiology of diseases. Here, we describe ExPheWas (exphewas.ca), a gene-based phenome-wide association study browser and platform that enables the conduct of gene-based Mendelian randomization. The ExPheWas data repository includes sex-stratified and sex-combined gene-based association results from 26 616 genes with 1746 phenotypes measured in up to 413 133 individuals from the U ...[more]

PMID: 35474380

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Project description:ObjectiveA multitude of observational studies have underscored a substantial comorbidity between COVID-19 and epilepsy. This study was aimed at establishing a conclusive causal link between these two conditions.MethodsWe employed Mendelian randomization (MR) to evaluate the causal link between COVID-19 and epilepsy, as well as its focal and generalized subtypes. The GWAS for epilepsy and its subtypes database were abstracted from both FinnGen consortium and ILAE. Additionally, we leveraged functional mapping and annotation (FUMA) to integrate information from genome-wide association studies (GWAS) results.ResultsThe MR analyses revealed that genetic liability to COVID-19 infection conferred a causal effect on epilepsy [FinnGen: OR: 1.5306; 95% confidence interval (CI): 1.1676-2.0062, PFDR (false discovery rate) = 0.0076; ILAE: OR: 1.3440; 95% CI: 1.0235-1.7649, PFDR = 0.0429], and generalized epilepsy (FinnGen: OR: 2.1155; 95% CI: 1.1734-3.8139, PFDR = 0.0327; ILAE: OR: 1.1245; 95% CI: 1.0444-1.2108, PFDR = 0.0114). Genetic liability to COVID-19 hospitalization conferred a causal effect on epilepsy (FinnGen: OR: 1.0934; 95% CI: 1.0097-1.1841, PFDR = 0.0422; ILAE: OR: 1.7381; 95% CI: 1.0467-2.8862, PFDR = 0.0451), focal epilepsy (ILAE: OR: 1.7549; 95% CI: 1.1063-2.7838, PFDR = 0.0338), and generalized epilepsy (ILAE: OR: 1.1827; 95% CI: 1.0215-1.3693, PFDR = 0.0406). Genetic liability to COVID-19 severity conferred a causal effect on epilepsy (FinnGen consortium: OR: 1.2454; 95% CI: 1.0850-1.4295, PFDR = 0.0162; ILAE: OR: 1.2724; 95% CI: 1.0347-1.5647, PFDR = 0.0403), focal epilepsy (FinnGen: OR: 1.6818; 95% CI: 1.1478-2.4642, PFDR = 0.0231; ILAE: OR: 1.6598; 95% CI: 1.2572-2.1914, PFDR = 0.0054), and generalized epilepsy (FinnGen: OR: 1.1486; 95% CI: 1.0274-1.2842, PFDR = 0.0335; ILAE: OR: 1.0439; 95% CI: 1.0159-1.0728, PFDR = 0.0086). In contrast, no causal linkage of epilepsy on COVID-19 was observed. Further, FUMA analysis identified six overlapping genes, including SMEK2, PNPT1, EFEMP1, CCDC85A, VRK2, and BCL11A, shared between COVID-19 and epilepsy. Tissue-specific expression analyses revealed that the disease-gene associations of COVID-19 were significantly enriched in lung, ovary, and spleen tissue compartments, while being significantly enriched in brain tissue for epilepsy.ConclusionOur study demonstrates that COVID-19 can be a contributing factor to epilepsy, but we found no evidence that epilepsy contributes to COVID-19.

Dataset Information

ExPheWas: a platform for cis-Mendelian randomization and gene-based association scans.

Publications

ExPheWas: a platform for cis-Mendelian randomization and gene-based association scans.

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