Omni2.5m beadchips

In ADNI, GWAS genotyping was performed using three different Illumina platforms, Illumina Human610-Quad, Illumina HumanOmni Express, and Ilumina Omni2.5M BeadChips (36 (link)). The APOE ε4 allele defining SNPs (rs429358, rs7412) were separately obtained using standard methods (36 (link)). Standard quality control procedures for genetic markers and subjects are performed as described previously: 1) for SNP, SNP call rate < 95%, Hardy-Weinberg equilibrium test p<1 × 10⁻⁶, and minor allele frequency (MAF) < 1%; 2) for subject, subject sex and identity check and subject call rate < 95% (37 (link)). Due to the impact of population stratification on association analysis, we select only non-Hispanic Caucasian participants using multidimensional scale analysis and HapMap GWAS genotypes (38 (link)). As the ADNI used different genotyping platforms, we impute ungenotyped SNPs separately in each platform using MACH (39 (link)) with the reference panel of the Haplotype Reference Consortium (HRC). After the imputation, we impose an r² = 0.30 as the threshold to accept the imputed genotypes. From the imputed data, we select 21 candidate AD SNPs (25 (link)) and 10 SNPs that have been associated with subcortical brain structures (27 ) based on a cut-off of p<1 × 10⁻⁷, listed in the Appendix.