There exist several limitations to this study. First, we did not consider Bonferroni correction for all possible multiple testing, primarily because we consider this study a replication of a positive association of this cluster with ND in an independent sample. A similar approach has been adopted by other researchers [25]. If we include correction for multiple testing, most detected associations of variants within this cluster with SI, SQ and SC at both the individual SNP and haplotype levels become non-significant, with the exceptions that rs951266 in CHRNA5 remained significant for SQ and rs11072768 in CHRNB4 for SI in the male sample (see Table 3). Similarly, we found that associations of four major haplotypes with SI and two major ones with SQ remained significant after Bonferroni correction for multiple testing of major haplotypes (Table 4). However, no significant associations of any SNPs or haplotypes with SC remained after Bonferroni correction for multiple testing. Also, we did not correct for our testing of two genetic models and three phenotypes, as they are highly related, which violates the assumption of independence for Bonferroni
