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Regarding rs3212986, this polymorphism is considered an important contributor to lung cancer development in smokers.22,23 In addition, no relation with never smokers was detected by Tau Yu et al.23 The NBN gene variant (rs1805794), located in MMR pathway, was also associated with an increased association with lung cancer in heavy smokers in accordance with Chuang et al.,24 though they only found association in male smokers

Results With never smokers as a reference, current smokers had a higher prevalence of trouble sleeping (OR = 1.931, 95% CI : 1.680, 2.219) and depression (OR = 2.525, 95% CI : 1.936, 3.293) as well as testosterone level ( = 0.083, 95% CI : 0.028, 0.140)

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Second, we did not apply additional pleiotropy-robust methods such as MR-PRESSO, which could help identify and correct for potential outlier variants, and thus we cannot completely rule out the presence of residual horizontal pleiotropy