but complementary questions. The SMA addressed the risk of initiation for the five phenotypes separately. Survival mixture models permit differentiation between subjects who never use (i.e., “long-term survivors”), and subjects who have initiated use or are likely to initiate use in the future. We compared survival models with or without a long-term survivor class, and with increasing constraints on how risk is modeled (no constraint, proportional hazard, and constant hazard). The SNPs are integrated as predictors of the risk of first use, and in case of the 2-class models, also as predictors of the difference between users and long-term survivors. The LCA, on the other hand, specifically focuses on differences in the pattern of initiation of tobacco, alcohol, cannabis, inhalants, and other substance use. The latent classes may for instance differentiate between subjects with an early versus a late onset of these substances. Alternatively, latent classes may also group subjects with a different pattern of initiation. For example, it may be possible to observe a class with an early age of initiation of alcohol and tobacco and a late first use of cannabis, versus a class with a reverse pattern of initiation. In the LCA models, SNPs were used to
