This study improved our coverage of an important gene family using a sample previously genotyped for a joint GWAS and large-scale candidate gene study (Bierut et al., 2007; Saccone et al., 2007a). Given the current popularity and importance of the GWAS design, the question of how best to interpret new analyses of GWAS datasets or samples in the context of the original large-scale GWAS is a challenge facing not only this study but the field as a whole. In the present case, although the NICSNP sample was used for a large-scale GWAS and candidate gene study, the CHRN gene family was in fact given the highest priority in our original design and would have been targeted even if our resources had been limited to only a few hundred SNPs. Therefore we feel it is appropriate and useful to report significant results based on multiple test correction for the 226 SNPs (111 r2 bins) tested here. However, these findings are not significant after formal multiple test correction for all the genotyping performed on this sample to date. In general, clearly citing any previous, overlapping GWAS or large-scale candidate gene studies is important to allow fully informed interpretation of results.
