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MendelVar: gene prioritization at GWAS loci using phenotypic enrichment of Mendelian disease genes
- Source :
- Bioinformatics, Sobczyk-Barad, M K, Gaunt, T R & Paternoster, L 2021, ' MendelVar : gene prioritization at GWAS loci using phenotypic enrichment of Mendelian disease genes ', Bioinformatics, vol. 37, no. 1, btaa1096, pp. 1-8 . https://doi.org/10.1093/bioinformatics/btaa1096
- Publication Year :
- 2021
- Publisher :
- Oxford University Press, 2021.
-
Abstract
- Gene prioritisation at GWAS loci necessities careful assembly and examination of different types of molecular evidence to arrive at a set of plausible candidates. In many human traits, common small-effect mutations may subtly dysregulate the function of the very same genes which are impacted by rare, large-effect mutations causing Mendelian disease of similar phenotype. However, information on gene-Mendelian disease associations, rare pathogenic mutations driving the disease, and the disease phenotype ontology is dispersed across many data sources and does not integrate easily with enrichment analysis.MendelVar is a new webserver facilitating transfer of knowledge from Mendelian disease research into interpretation of genetic associations from GWAS of complex traits. MendelVar allows querying of pre-defined or LD-determined genomic intervals against a comprehensive integrated database to find overlap with genes linked to Mendelian disease. Next, MendelVar looks for enrichment of any Human Phenotype Ontology, Disease Ontology and other ontology/pathway terms associated with identified Mendelian genes. In addition, MendelVar provides a list of all overlapping pathogenic and likely pathogenic variants for Mendelian disease sourced from ClinVar.Inclusion of information obtained from MendelVar in post-GWAS gene annotation pipelines can strengthen the case for causal importance of some genes. Moreover, as genes with Mendelian disease evidence may make for more successful drug targets, this may be particularly useful in drug discovery pipelines. Taking GWAS summary statistics for male-pattern baldness, intelligence and atopic dermatitis, we demonstrate the use of MendelVar in prioritizing candidate genes at these loci which are linked to relevant enriched ontology terms. MendelVar is freely available athttps://mendelvar.mrcieu.ac.uk/
- Subjects :
- Statistics and Probability
Linkage disequilibrium
Candidate gene
AcademicSubjects/SCI01060
Locus (genetics)
Genome-wide association study
Disease
Computational biology
Mendelian
Biology
Biochemistry
Polymorphism, Single Nucleotide
Linkage Disequilibrium
03 medical and health sciences
symbols.namesake
0302 clinical medicine
Disease Ontology
Human Phenotype Ontology
GWAS
Humans
Molecular Biology
Gene
030304 developmental biology
0303 health sciences
030305 genetics & heredity
Molecular Sequence Annotation
Gene Annotation
bioinformatics
Genome Analysis
Phenotype
Original Papers
Computer Science Applications
Computational Mathematics
Computational Theory and Mathematics
Diabetes Mellitus, Type 2
Mendelian inheritance
symbols
030217 neurology & neurosurgery
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- ISSN :
- 13674811 and 13674803
- Volume :
- 37
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Bioinformatics
- Accession number :
- edsair.doi.dedup.....bf89044a585b26b817bad1eeebd0e1d0