Even by leveraging meta-analytically identified SNPs, the present sample was not large enough to identify developmental changes in individual SNP effects but, rather, SNPs had to be combined into a single genetic risk score before the effect was large enough to be detectable and testable in this sample. This score appears to be biologically coherent, in that the effects tagged by the SNPs are relevant to either nicotine metabolism or nicotine transmission. Future work may do better by combining scores within explicit biological pathways through the use of pathway databases (Vink, et al., 2009). In this way, genetic scores take on more refined biological meaning and results provide clearer theoretical import. A major challenge to the pathway approach is simply in identifying enough SNPs or other genetic variants within a pathway that have measureable effects on the phenotype. While non-trivial and etiologically informative, it is very unlikely that this SNP score could be utilized in any way in a personalized medicine context. There are many theories as to why no sizable genetic effects have been discovered for complex traits (Manolio,
