the trait residuals (adjusted for age and sex) on the number of minor alleles at each SNP, with empirical P-values estimated by permutation to avoid issues with the test statistic distribution caused by the combination of rare variants and slight deviations from normality in the phenotypes. All association analyses were performed using PLINK.56 Mark-recapture analysis followed the Lincoln-Petersen and Modified Petersen methods57, 58 with 95% confidence intervals calculated following Chapman.59 Burden analysis was performed in PLINK/SEQ to implement BURDEN and VTTEST with empirical P-values estimated using permutation. Genotyping of the replication and familial samples was performed by the Edinburgh Wellcome Trust Clinical Research Facility Genetics Core using TaqMan SNP genotyping assay C__33950433_10 with concurrent genotyping of known heterozygotes.
