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Integrating GWAS and Expression Data for Functional Characterization of Disease-Associated SNPs: An Application to Follicular Lymphoma

2012; Elsevier BV; Volume: 92; Issue: 1 Linguagem: Inglês

10.1016/j.ajhg.2012.11.009

1537-6605

Lucía Conde, Paige M. Bracci, Rhea Richardson, Stephen B. Montgomery, Christine F. Skibola,

RNA Research and Splicing

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.