The primary focus was to test variants with MAF≥1%, as these will be imputed with high confidence. The statistical significance threshold applied to meta-analysis of all variants with MAF≥1% was 5×10−8, consistent with widespread convention in GWAS of European individuals. Since our imputation procedure is expected to provide some marginal level of accuracy down to MAF of 0.1%, we also conducted an exploratory association test for low frequency variants with 0.1%<MAF<1%, to which we applied a statistical significance threshold of p<5×10−9. Only two such low-frequency variants surpassed the conventional common variant threshold of p<5×10−8. Of these two, one low-frequency variant, associated with SmkInit, survived the more stringent multiple testing correction (rs181508347, intergenic, MAF=.0096, p=5×10−10), and is included in our count of discovered loci and included in Supplementary Table 4. The more stringent threshold applies a correction for ~10 million tests, which is approximately the number of conditionally independent variants tested once the MAF lower bound was extended from 1% to 0.1%. We calculated this threshold using three existing methods60–62. These methods make use of the eigenvalues of the matrix of
