Simulations showed that large sample sizes of the discovery sample are necessary (50). A strength of the present study is that summary-level results of the TAG meta-analyses were used as discovery sample. The TAG meta-analyses is currently the largest GWA meta-analyses for smoking behavior. The chances of success of polygenic risk score analyses depend primarily on the size of the discovery set. If the sample size is too small, the risk profiles will be based on random noise and are not expected to explain variance in the target set (31,50,52).