Integrating GWAS and expression data for functional characterization of disease-associated SNPs: an application to follicular lymphoma.
Am J Hum Genet
; 92(1): 126-30, 2013 Jan 10.
Article
en En
| MEDLINE
| ID: mdl-23246294
ABSTRACT
Development of post-GWAS (genome-wide association study) methods are greatly needed for characterizing the function of trait-associated SNPs. Strategies integrating various biological data sets with GWAS results will provide insights into the mechanistic role of associated SNPs. Here, we present a method that integrates RNA sequencing (RNA-seq) and allele-specific expression data with GWAS data to further characterize SNPs associated with follicular lymphoma (FL). We investigated the influence on gene expression of three established FL-associated loci-rs10484561, rs2647012, and rs6457327-by measuring their correlation with human-leukocyte-antigen (HLA) expression levels obtained from publicly available RNA-seq expression data sets from lymphoblastoid cell lines. Our results suggest that SNPs linked to the protective variant rs2647012 exert their effect by a cis-regulatory mechanism involving modulation of HLA-DQB1 expression. In contrast, no effect on HLA expression was observed for the colocalized risk variant rs10484561. The application of integrative methods, such as those presented here, to other post-GWAS investigations will help identify causal disease variants and enhance our understanding of biological disease mechanisms.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Linfoma Folicular
/
Polimorfismo de Nucleótido Simple
/
Estudio de Asociación del Genoma Completo
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Am J Hum Genet
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos