Annotating genetic variants to target genes using H-MAGMA.
Nat Protoc
; 18(1): 22-35, 2023 01.
Article
em En
| MEDLINE
| ID: mdl-36289406
ABSTRACT
An outstanding goal in modern genomics is to systematically predict the functional outcome of noncoding variation associated with complex traits. To address this, we developed Hi-C-coupled multi-marker analysis of genomic annotation (H-MAGMA), which builds on traditional MAGMA-a gene-based analysis tool that assigns variants to their target genes-by incorporating 3D chromatin configuration in assigning variants to their putative target genes. Applying this approach, we identified key biological pathways implicated in a wide range of brain disorders and showed its utility in complementing other functional genomic resources such as expression quantitative trait loci-based variant annotation. Here, we provide a detailed protocol for generating the H-MAGMA variant-gene annotation file by using chromatin interaction data from the adult human brain. In addition, we provide an example of how H-MAGMA is run by using genome-wide association study summary statistics of Parkinson's disease. Lastly, we generated variant-gene annotation files for 28 tissues and cell types, with the hope of contributing a resource for researchers studying a broad set of complex genetic disorders. H-MAGMA can be performed in <2 h for any cell type in which Hi-C data are available.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Genômica
/
Estudo de Associação Genômica Ampla
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article