The twins in this study were initially ascertained through the Australian Twin Registry, followed by cascading recruitment of non-twin siblings, parents, adult offspring and spouses12. Data from 6166 subjects of European descent were used for replication analysis with the SC. Detailed characteristics of this sample and genotyping platform were described in Heath et al.12. Imputed dosage data were obtained using MACH (http://www.sph.umich.edu/csg/abecasis/MACH). The association of individual SNPs with SC was performed using PROC GLIMMIX from SAS. Age and gender were included as covariates for association analysis. The GEE model described above was used for the association analysis with AD.