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It has been demonstrated that using cigarettes per day as an intermediate variable in Mendelian randomisation analyses using rs16969968/rs1051730 can lead to large biases in causal effect size estimates.51 The rs16969968/rs1051730 variant associates with smoking heaviness within smokers but is not an instrument for smoking status (ever smoking vs never smoking).29 Therefore we cannot rule out the possibility that being a smoker, rather than smoking heaviness could influence likelihood of depression or anxiety

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