Genome-wide association study of follicular lymphoma identifies a risk locus at 6p21.32

Abstract

To identify susceptibility loci for non-Hodgkin lymphoma subtypes, we conducted a three-stage genome-wide association study. We identified two variants associated with follicular lymphoma at 6p21.32 (rs10484561, combined P = 1.12 x 10(-29) and rs7755224, combined P = 2.00 x 10(-19); r(2) = 1.0), supporting the idea that major histocompatibility complex genetic variation influences follicular lymphoma susceptibility. We also found confirmatory evidence of a previously reported association between chronic lymphocytic leukemia/small lymphocytic lymphoma and rs735665 (combined P = 4.24 x 10(-9)).

Figure 1. LD and association results for the FL-associated regions in the major histocompatibility complex (MHC)

In the main panel, trend p-values (as -log₁₀) are shown for SNPs genotyped in the MHC region between positions 30,000Mb and 35,000Mb, where two independent FL-associated peaks were found. The first peak, represented by rs6457327 (in yellow), is located at 6p21.33 in the MHC Class I region. The second independent peak, represented by rs10484561 (in green), is located at 6p21.32 in the MHC Class II region. The secondary panel shows the SNPs genotyped (in black) and imputed (in red) in Stage 1 in a 500kb region centered on rs10484561 at 6p21.32. Imputations were based on data from HapMap Phase II release #22 in CEU population. Figure constructed using the snp.plotter R package (http://cbdb.nimh.nih.gov/∼kristin/snp.plotter.html).