Mendelian Randomization is a technique by which one can use genetic variation as a proxy for environmental exposure, and has been the subject of several reviews (Ebrahim & Smith, 2008; Smith, 2011). In the present study we use genetic variation associated with nicotine use as a proxy for the environmental exposure to nicotine. That is, individuals with high-risk genetic variation will be more likely to smoke more cigarettes. If the extent of nicotine use causes later alcohol use (a plausible prediction to be made from the gateway model), then we expect these nicotine-relevant variants to also be associated with alcohol use, even though the strength of the relationship may be attenuated to the extent expected from the less than perfect correlation between alcohol and nicotine use. All alcohol analyses were conducted in the same way as described for nicotine above.
