The unfiltered dataset obtained from dbGaP contained 599,156 unique SNPs. The Perlegen genotyping algorithm yielded a quality score for each individual genotype, and a more stringent quality score cutoff (≥ 10) than that used by Perlegen was applied. The SNP quality control process is described in detail in the Supplemental Methods. Briefly, to be included in the final analysis dataset, SNPs were required not to have any of the following features: gross mapping problem (37), ≥2 genotype disagreements in 40 duplicated samples, ≥2 Mendelian inheritance errors in 38 complete trio samples, minor allele frequency <0.01, or >0.05 missing genotypes in either cases or controls. A Hardy-Weinberg filter was not used as lack of fit to Hardy-Weinberg expectations can occur for valid reasons (e.g., a true association) (38) and given that 95.6% (=51,592/53,994) of SNPs with p<0.00001 from an exact test of Hardy-Weinberg equilibrium (39) in controls were already flagged for exclusion. A total of 435,291 SNPs met these criteria and were included in the final analysis dataset (included as a Supplemental File, “mddC.bim”). Additional quality control checks are described in
