Common variation at 3q26.2, 6p21.33, 17p11.2 and 22q13.1 influences multiple myeloma risk

Abstract

To identify variants for multiple myeloma risk, we conducted a genome-wide association study with validation in additional series totaling 4,692 individuals with multiple myeloma (cases) and 10,990 controls. We identified four risk loci at 3q26.2 (rs10936599, P = 8.70 × 10(-14)), 6p21.33 (rs2285803, PSORS1C2, P = 9.67 × 10(-11)), 17p11.2 (rs4273077, TNFRSF13B, P = 7.67 × 10(-9)) and 22q13.1 (rs877529, CBX7, P = 7.63 × 10(-16)). These data provide further evidence for genetic susceptibility to this B-cell hematological malignancy, as well as insight into the biological basis of predisposition.

Figure 1. Regional plots of association results and recombination rates for the 3q26.2, 6p21.33, 17p11.2 and 22q13.1 susceptibility loci.

(a-d) Association results of both genotyped (triangles) and imputed (circles) SNPs in the GWAS samples and recombination rates for rates within the four loci: 3q26.2, 6p21.33, 17p11.2 and 22q13.1. For each plot, −log₁₀ P values (y axis) of the SNPs are shown according to their chromosomal positions (x axis). The top genotyped SNP in each combined analysis is a large triangle and is labeled by its rsID. The color intensity of each symbol reflects the extent of LD with the top genotyped SNP: white (r²=0) through to dark red (r²=1.0). Genetic recombination rates (cM/Mb), estimated using HapMap CEU samples, are shown with a light blue line. Physical positions are based on NCBI build 36 of the human genome. Also shown are the relative positions of genes and transcripts mapping to each region of association. Genes have been redrawn to show the relative positions; therefore, maps are not to physical scale. The lower panel shows the region of interest together with all transcripts and chromatin state segmentation track (ChromHMM) for lymphoblastoid cells using data from the HapMap Encode Project.