Common variation at 6p21.31 (BAK1) influences the risk of chronic lymphocytic leukemia

Abstract

We performed a meta-analysis of 3 genome-wide association studies to identify additional common variants influencing chronic lymphocytic leukemia (CLL) risk. The discovery phase was composed of genome-wide association study data from 1121 cases and 3745 controls. Replication analysis was performed in 861 cases and 2033 controls. We identified a novel CLL risk locus at 6p21.33 (rs210142; intronic to the BAK1 gene, BCL2 antagonist killer 1; P = 9.47 × 10(-16)). A strong relationship between risk genotype and reduced BAK1 expression was shown in lymphoblastoid cell lines. This finding provides additional support for polygenic inheritance to CLL and provides further insight into the biologic basis of disease development.

Figure 1

Lower BAK1 expression associated with the G allele of rs210134 in lymphoblastoid cell lines. We assessed the correlation between normalized BAK1 gene expression and the count of the G allele of rs210134 using Spearman rank correlation and publicly available Sentrix Human-6 Expression BeadChips (Illumina) data on 156 lymphoblastoid cell lines derived from healthy female twins as part of the MuTHER project as of December 15, 2008 (GENEVAR project). The G allele is associated with the elevated risk of CLL.