Follow-up of the replicated SNVs in the literature and eQTL databases implicated some potentially interesting genes: NT5C2 is known to hydrolyse purine nucleotides and be involved in maintaining cellular nucleotide balance, and was previously associated with schizophrenia [62]. REV3L, encodes the catalytic subunit of DNA polymerase ζ (zeta) which is involved in translesion DNA synthesis. Previously, polymorphisms in a microRNA target site of REV3L were shown to be associated with lung cancer susceptibility [63]. We showed that decreased expression of REV3L may also lower the probability of smoking initiation. The SNV, rs11776293, intronic in EPHX2, was associated with reduced SI in the combined meta-analysis, and is in LD with rs56372821 (r2 = 0.83), which is associated with reduced cannabis use disorder [64]. rs216195 (in SMG6) was genome-wide significant in the discovery and the combined meta-analysis. SMG6 is a plausible candidate gene as it was previously shown to be less methylated in current smokers compared to never smokers [65]. The combined meta-analysis also identified a rare missense variant in CCDC141, rs150493199 (MAF < 0.01; Table 2). Coding variants in CCDC141 were previously associated with heart rate [66] and blood pressure [67, 68].
