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A recent genome-wide association study of chronic lymphocytic leukaemia (CLL) has identified a susceptibility locus on 6p25.3 associated with a modest but highly significant increase in CLL risk. Using a set of single nucleotide polymorphism (SNP) markers, we generated a fine-scale map and narrowed the association signal to a 18 kb DNA segment within the 3′-untranslated region (UTR) of the  IRF4  (interferon regulatory factor 4) gene. Resequencing this segment in European subjects identified 55 common polymorphisms, including 13 highly correlated candidate causal variants. In a large case–control study, it was shown that all but four variants could be excluded with 95% confidence. These four SNPs map to a 3 kb region of the 3′-UTR of  IRF4 , consistent with the causal basis of the association being mediated through differential  IRF4  expression.

Fine-scale mapping of the 6p25.3 chronic lymphocytic leukaemia susceptibility locus