MendelVar: gene prioritization at GWAS loci using phenotypic enrichment of Mendelian disease genes

• Published in: Bioinformatics (Oxford, England) Vol. 37; no. 1; p. 1
• Main Authors: Sobczyk, M K, Gaunt, T R, Paternoster, L
• Format: Journal Article
• Language: English
• Published: England 09-04-2021
• Subjects: Diabetes Mellitus, Type 2; Genome-Wide Association Study; Humans; Linkage Disequilibrium; Molecular Sequence Annotation; Phenotype; Polymorphism, Single Nucleotide
• ISSN: 1367-4811
• DOI: 10.1093/bioinformatics/btaa1096

Gene prioritization at human GWAS loci is challenging due to linkage-disequilibrium and long-range gene regulatory mechanisms. However, identifying the causal gene is crucial to enable identification of potential drug targets and better understanding of molecular mechanisms. Mapping GWAS traits to known phenotypically relevant Mendelian disease genes near a locus is a promising approach to gene prioritization.
We present MendelVar, a comprehensive tool that integrates knowledge from four databases on Mendelian disease genes with enrichment testing for a range of associated functional annotations such as Human Phenotype Ontology, Disease Ontology and variants from ClinVar. This open web-based platform enables users to strengthen the case for causal importance of phenotypically matched candidate genes at GWAS loci. We demonstrate the use of MendelVar in post-GWAS gene annotation for type 1 diabetes, type 2 diabetes, blood lipids and atopic dermatitis.
MendelVar is freely available at https://mendelvar.mrcieu.ac.uk.
Supplementary data are available at Bioinformatics online.