Second, genotyping coverage varied between studies, and several studies in our meta-analysis had only a few variants genotyped. As a result, not all sub-bins were tested and the sample size varied across the tested sub-bins. For example, SNP rs55853698 which was imputed and reported as highly associated with smoking quantity in a previous meta-analysis of European ancestry subjects [Liu, et al. 2010], lies in bin A, but no genotyping data was available for testing this SNP or the sub-bin it represents in Asian and African American populations. Use of imputed data has the potential to mitigate these problems. However, imputation was not possible for our low-coverage studies. Therefore, the concerns about having untested SNPs and unequal subjects in the region would remain even with imputed data. We believe it is important to report our findings based on directly genotyped variants, and the interpretation of the consistent associations is not expected to change with imputation.
