An example of biological prioritization that could be interpreted as a ‘success’ is the following discovery of a novel genetic association with nicotine dependence. In Saccone et al. (28) the investigators conducted a large candidate gene study of nicotine dependence. Although there were no statistically significant results after correcting for multiple testing, the fifth smallest P-value was the missense SNP rs16969968 in the nicotinic receptor gene CHRNA5 and was highlighted as the most promising signal. A GWAS of nicotine dependence (29) was conducted in conjunction with the candidate gene study, and although the missense SNP ranked 199 in the combined GWAS/candidate gene results, it was the top priority for further study in the overall project. It has since been replicated in numerous studies of nicotine dependence, heavy smoking, lung cancer and COPD (30–36), including three very large meta-analytic studies (24–26). Furthermore, there have been very few replicated associations other than the original SNP and some SNPs in nearby genes. Clearly this example alone is not evidence of the general predictive power of biological information, in this case a missense SNP
