Two of our novel signals of association with smoking behaviour implicate NCAM1; one SNP lies within an intron of NCAM1 and a second variant, located distantly on chromosome 2, is a trans eQTL for NCAM1 in brain tissue (medulla)—ie, it is associated with the level of expression of NCAM1. This second SNP is also a trans eQTL in substantia nigra tissue for another gene called WDR61, which is close to the genes CHRNA3 and CHRNA5 at 15q25—a locus strongly associated with smoking behaviour.17–19 The substantia nigra plays an important part in reward and addiction,48 but little is known about WDR61 other than that expression can be induced by mechanical strain in mesenchymal stem cells.49
