Until now, the only common DNMT3B variant implicated by GWAS was identified in a study of inflammatory bowel disease (IBD; intronic rs4911259). This SNP was associated with nicotine dependence in our meta-analysis (P=3.5×10−6) and is in LD with our top SNP rs910083 (r2=0.76 and D′=1 in 1000G EUR, r2=0.16 and D′=1 in 1000G AFR).65 Cigarette smoking is the environmental factor most consistently associated with IBD,66 and these shared SNP association signals suggest that DNMT3B SNPs may exert pleiotropic effects. Alternatively, it is possible that smoking mediates the DNMT3B SNP association with IBD, but the IBD GWAS did not include adjustment for smoking.65
