Novel variants in novel genes were also prioritized at high resolution. To take the most statistically compelling examples in Table 1, we found rs28929474, a low frequency nonsynonymous variant in SERPINA1, associated with DrnkWk (MAF=.02; PPA=1.0 and .95). When homozygous, the alternate T (allele frequency = .02; frequency of TT genotype under Hardy Weinberg = 4 in 10,000) allele is a leading cause of alpha-1 antitrypsin deficiency. Here, we find the same risk allele, the T allele, is associated with an approximately .05 standard deviation decrease in drinks per week. We also discovered rs35891966, a variant in NAV2, associated with SmkInit (MAF=.07; PPA = 1.0 and .98) at single base-pair resolution. NAV2 is involved in neuronal development and previously shown to be differentially expressed between smokers and non-smokers, but not previously implicated in GWAS(59).
