The two loci mapping to chromosomes 2q21and 6p21showed evidence of association with age at smoking initiation at a suggestive genome-wide significance level, using both HapMap II and 1000 Genomes projects reference imputation panels. The association peaks found here do not localize within any known genes, suggesting distant regulation of yet unidentified target genes may be involved. SNPs from chromosome 6p21 are located close to the Human Leukocyte Antigen locus, and ZBTB9 and BAK1 are the closest genes to the association peak. The BAK1 gene, encoding a proapoptotic protein, has been previously associated by GWAS with testicular germ cell tumors 37 and platelet number.38 Yet SNPs identified in these studies do not correlate, in terms of LD, with top SNPs from our age at smoking initiation GWAS.
