Three recent GWASs suggested a strong association between variants of CHRNA5/A3/B4 (encoding subunits α5, α3, and β4) at 15q24 and lung cancer.46–48 However, although one study revealed a significant association of a CHRNA3 SNP with ND,48 the other two studies suggested association of this and other variants with lung cancer independent of their association with smoking.46,47 Several other studies provide independent verification of the association between this gene cluster and ND,49–51 and suggest that power, precision of phenotyping, or severity may explain the apparent association with lung cancer rather than a direct, smoking-independent association. We feel that a biological link between variants in the CHRNA5/A3/B4 cluster and ND is more plausible than a direct effect of these variants on lung cancer.
