By contrast, no significant association of CHRNB2, which encodes the β2 subunit, with ND was reported in four independent studies (e.g., see 35,36), except for a significant association of rs2072661 in the 3′-UTR of the gene with ability to quit smoking.38 However, epistatic analysis using a generalized MULTIFACTOR DIMENSIONALITY REDUCTION METHOD39 revealed that CHRNB2 has a significant effect on ND when analyzed with CHRNA4 together.40 The failure to detect significant association of CHRNB2 with ND by itself may thus be attributable to the relatively small effect of CHRNB2 or strong dependency of CHRNB2 effects on specific CHRNA4 variants. More importantly, detection of significant interaction of CHRNB2 with CHRNA4 in humans is consistent with the formation of functional nAChRs with these two subunits.41,42 A moderate association of CHRNB2 with early response to alcoholism has also been reported.43
