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

M K Sobczyk-Barad; T R Gaunt; L Paternoster

doi:10.1093/bioinformatics/btaa1096

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

M K Sobczyk-Barad^*, T R Gaunt, L Paternoster

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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Abstract

Motivation
Gene prioritisation 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 prioritisation.

Results
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.

Original language	English
Article number	btaa1096
Pages (from-to)	1-8
Number of pages	8
Journal	Bioinformatics
Volume	37
Issue number	1
DOIs	https://doi.org/10.1093/bioinformatics/btaa1096
Publication status	Published - 9 Apr 2021

Bibliographical note

Publisher Copyright:
© The Author(s) 2021. Published by Oxford University Press.

Keywords

GWAS
bioinformatics
Mendelian

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title = "MendelVar: gene prioritization at GWAS loci using phenotypic enrichment of Mendelian disease genes",

abstract = "MotivationGene prioritisation 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 prioritisation.ResultsWe 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. ",

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author = "Sobczyk-Barad, {M K} and Gaunt, {T R} and L Paternoster",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2021. Published by Oxford University Press.",

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doi = "10.1093/bioinformatics/btaa1096",

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AU - Gaunt, T R

AU - Paternoster, L

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Y1 - 2021/4/9

N2 - MotivationGene prioritisation 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 prioritisation.ResultsWe 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.

AB - MotivationGene prioritisation 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 prioritisation.ResultsWe 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.

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

Abstract

Bibliographical note

Keywords

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