In this data set, QTDT finds no evidence for stratification therefore we performed QTDT-total test to evaluate the total evidence for association. Several SNPs show significant association with AAO of daily smoking (Table 2). The most significantly associated variant is rs1996371, located upstream of the CHRNB4 gene (p = 0.002). Individuals homozygous for the risk allele had AAO at least one year earlier than individuals who are homozygous for the non-risk allele; the difference in AAO between these two groups was statistically significant (p = 0.0002; Table 3). Variants rs11634351 and rs922692 that are highly correlated with rs1996371 (r2 = 0.98 and r2 = 0.95, respectively) also show association with AAO of daily smoking. Conditional analysis showed that association of rs1996371 and correlated SNPs with AAO of daily smoking is independent of rs16969968 (Table 2). Conditional analysis using variants rs578776 and rs880395, which represent other distinct loci in this gene cluster produced similar results and confirmed the independent relationship of rs1996371 (p<0.005). Variants rs1996371 and rs922692 withstood the conservative Bonferroni correction (<0.005). Because most of the markers used in this
