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Chunk #52 — Limitations

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The CHRNA5/A3/B4 gene cluster and tobacco, alcohol, cannabis, inhalants and other substance use initiation: replication and new findings using mixture analyses.
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Regarding the reliability of the results concerning individual SNPs, some caution is warranted. In samples of limited size, small changes in observed allele frequencies due to sampling fluctuation can substantially affect results (Duncan and Keller 2011). Furthermore, multi-collinearity can render individual effects unreliable, although importantly, the joint prediction of correlated predictors is asymptotically correct. All analyses presented in the results included all family members, and the models were fitted using a sandwich-type estimator with family id as the clustering variable. We conducted additional analyses with only one subject per family. The additional analyses did not change our main conclusions, although the decrease in sample size rendered some of the significant effects non-significant. Also, not all of the individual SNP effects coincided.