Joint genetic analysis using variant sets reveals polygenic gene-context interactions.
PLoS Genet
; 13(4): e1006693, 2017 04.
Article
em En
| MEDLINE
| ID: mdl-28426829
ABSTRACT
Joint genetic models for multiple traits have helped to enhance association analyses. Most existing multi-trait models have been designed to increase power for detecting associations, whereas the analysis of interactions has received considerably less attention. Here, we propose iSet, a method based on linear mixed models to test for interactions between sets of variants and environmental states or other contexts. Our model generalizes previous interaction tests and in particular provides a test for local differences in the genetic architecture between contexts. We first use simulations to validate iSet before applying the model to the analysis of genotype-environment interactions in an eQTL study. Our model retrieves a larger number of interactions than alternative methods and reveals that up to 20% of cases show context-specific configurations of causal variants. Finally, we apply iSet to test for sub-group specific genetic effects in human lipid levels in a large human cohort, where we identify a gene-sex interaction for C-reactive protein that is missed by alternative methods.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Locos de Características Quantitativas
/
Epistasia Genética
/
Estudo de Associação Genômica Ampla
/
Interação Gene-Ambiente
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article