Exploiting the GTEx resources to decipher the mechanisms at GWAS loci.
Genome Biol
; 22(1): 49, 2021 01 26.
Article
in En
| MEDLINE
| ID: mdl-33499903
The resources generated by the GTEx consortium offer unprecedented opportunities to advance our understanding of the biology of human diseases. Here, we present an in-depth examination of the phenotypic consequences of transcriptome regulation and a blueprint for the functional interpretation of genome-wide association study-discovered loci. Across a broad set of complex traits and diseases, we demonstrate widespread dose-dependent effects of RNA expression and splicing. We develop a data-driven framework to benchmark methods that prioritize causal genes and find no single approach outperforms the combination of multiple approaches. Using colocalization and association approaches that take into account the observed allelic heterogeneity of gene expression, we propose potential target genes for 47% (2519 out of 5385) of the GWAS loci examined.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Gene Expression
/
Genetic Predisposition to Disease
/
Genome-Wide Association Study
/
Genotype
Limits:
Humans
Language:
En
Journal:
Genome Biol
Journal subject:
BIOLOGIA MOLECULAR
/
GENETICA
Year:
2021
Document type:
Article
Affiliation country:
United States
Country of publication:
United kingdom