We also located statistically significant signal coming from the known HLA locus on chromosome 6, result suggesting a link between smoking and the immune system. Loci in the HLA region have been previously implicated in e.g., schizophrenia32, with which smoking dependence shares genetic vulnerabilities. Three genomic loci were significantly associated with ever smoking. The top signal came from the noncoding antisense RNA transcript BDNF-AS locus (P=6.25E-07) on chromosome 11. BDNF-AS downregulates the BDNF gene 33 which in turn has a key role in regulating neuronal growth and synaptic plasticity 33, 34. The BDNF gene did not reach genome-wide significance in our gene-based analysis (P=1.3E-04), result indicating that the eight significant SNPs reported in the combined TAG analysis were tagging better the overlapping non-coding RNA BDNF-AS locus (see Supplementary Figures 35 for LD information).
