European-based polygenic risk score and genome-wide association study of B-cell non-Hodgkin lymphoma subtypes in Israeli Jews and Palestinian Arabs

Among individuals of European Ancestry (EA), genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) and polygenic risk scores (PRSs) associated with non-Hodgkin lymphoma (NHL) risk. We evaluated subtype-specific PRSs, based on established EA-SNPs, in Israeli Jews (IJ) and Palestinian Arabs (PA) and performed a GWAS in the combined ethnic groups to identify new loci. We included three common pathologically confirmed subtypes: diffuse large B-cell (DLBCL), follicular (FL) and marginal zone (MZL) lymphomas. Controls were frequency matched to cases by age and sex. Among 752 IJ (201—DLBCL; 130—FL; 54—MZL/367—controls) and 593 PA (203—DLBCL; 41—FL/349-controls), we computed PRSs weighted by EA-derived effect estimates and used logistic regression models adjusted for confounders. In the combined ethnic groups of IJ and PA, subtype-specific PRSs were significantly associated with the corresponding subtype, with a 1.69-fold, 2.21-fold and 2.26-fold risk for DLBCL, FL and MZL, respectively; however, these effect sizes were attenuated compared to those reported in EA and varied by ethnicity. In the GWAS of the combined ethnic groups, two novel SNPs in the 6p21.32 locus were associated with DLBCL risk. Additional GWAS studies are needed among Jewish and Arab populations to improve genetic risk prediction for NHL in these ethnic groups.