MRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol BS8 2BN, UK.
Bioinformatics. 2021 Apr 9;37(1):1-8. 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.
由于连锁不平衡和长程基因调控机制，人类 GWAS 基因座的基因优先级划分具有挑战性。然而，确定因果基因对于确定潜在的药物靶点和更好地了解分子机制至关重要。将 GWAS 特征映射到基因座附近已知表型相关的 Mendelian 疾病基因是一种很有前途的基因优先级划分方法。
我们提出了 MendelVar，这是一个全面的工具，它整合了来自四个 Mendelian 疾病基因数据库的知识，并对一系列相关的功能注释进行富集测试，如人类表型本体、疾病本体和 ClinVar 中的变体。这个开放的基于网络的平台使研究人员能够加强 GWAS 基因座上与表型匹配的候选基因因果重要性的证据。我们展示了 MendelVar 在 1 型糖尿病、2 型糖尿病、血脂和特应性皮炎的 GWAS 后基因注释中的应用。
MendelVar 可在 https://mendelvar.mrcieu.ac.uk 免费获得。
补充数据可在《Bioinformatics》在线获取。
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