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Chunk #26 — Discussion

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A GABRA2 polymorphism improves a model for prediction of drinking initiation.
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There are several potential limitations to this study. First, the majority of subjects were offspring/descendants of the original COGA high-risk families, which may limit the ability to generalize the results to other populations. Second, due to the number of subjects as well as multiple testing issues, we did not perform a genome-wide association study (GWAS) that specifically identified GABRA2 rs279871 as the best choice for inclusion in the model. Third, although several studies have identified both the minor and major alleles of SNPs in this region to be the risk allele for alcohol dependence, two meta-analyses of these publications (Li et al., 2014; Zintzaras, 2012) found the less common allele to be the risk allele. Additionally, both meta-analyses report the distribution of the risk allele to be in the opposite directions for EA compared to AA subjects. Fourth, while there are no gender differences in our model's prediction of age of first drink (similar to Miech, Johnston, O'Malley, Bachman, & Schulenberg, 2016), this may be limited by our use of this covariate as a binary variable; our sample size is