For the genotyped SNPs in our AA replication sample, the PedCheck program was used to determine genotyping consistency for Mendelian inheritance (26). Pair-wise linkage disequilibrium (LD) between all SNP markers was assessed using Haploview (27), with the determination of haplotype blocks based on block definitions proposed by Gabriel and colleagues (28). Association between individual SNPs and the ND measures (SQ, HSI and FTND) was determined by the PBAT program using generalized estimating equations (29), with gender and age entered as covariates. The association test was allele-based. Associations between each ND measure and haplotypes from multiple SNP combinations were examined using the FBAT program, with the computation of p values for the Z statistic based on the Monte Carlo sampling option under the null distribution of no linkage and no association (30). The haplotype analysis was single haplotype-based. Since four major haplotypes were tested, the significance for the analysis was set at 0.0125 (=0.05/4) adjusting multiple testing through Bonferroni correction.
