title: Integrating GWAS and expression data for functional characterization of disease-associated SNPs: an application to follicular lymphoma.
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.
authors.affiliation: Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, Berkeley, CA 94720-7360, USA.
authors.forename: Lucia
authors.initials: L
authors.lastname: Conde
authors.forename: Paige M
authors.initials: PM
authors.lastname: Bracci
authors.forename: Rhea
authors.initials: R
authors.lastname: Richardson
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Montgomery
authors.forename: Christine F
authors.initials: CF
authors.lastname: Skibola
mesh_terms: D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D055106:Genome-Wide Association Study; D006680:HLA Antigens / Q000378:metabolism; D006801:Humans; D015810:Linkage Disequilibrium; D008224:Lymphoma, Follicular / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D006680:HLA Antigens