Sequence Kernel Association Test (SKAT) (Wu et al., 2011) was adopted to test for association between the 11 RVs and three SD phenotypes, namely, AD, CD and OD. When one SD phenotype was used as the outcome, the other two phenotypes were adjusted in the model along with sex and age. SKAT is a powerful method to test for association between SNP sets and phenotypes, and is designed to perform well when the SNP set is a mixture of protective and deleterious variants (Ladouceur et al., 2012). At first, SKAT analyses were performed for RVs in the same genes. Since these 11 RVs are located in 7 genes, and there were three phenotypes and two populations, the threshold of significance was 0.05/(7×3×2)=0.0012. Then, all 11 RVs were analyzed together to test whether genes in the NMDAR system associated with AD, CD or OD. Bonferroni correction was used here also to adjust for multiple comparisons, and the threshold of significance was 0.05/(3×2)=0.0083.
