Integrating GWAS and expression data for functional characterization of disease-associated SNPs: an application to follicular lymphoma

Am J Hum Genet. 2013 Jan 10;92(1):126-30. doi: 10.1016/j.ajhg.2012.11.009. Epub 2012 Dec 13.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic
  • Genome-Wide Association Study*
  • HLA Antigens / metabolism
  • Humans
  • Linkage Disequilibrium
  • Lymphoma, Follicular / genetics*
  • Polymorphism, Single Nucleotide*


  • HLA Antigens