Brain APOE expression quantitative trait loci-based association study identified one susceptibility locus for Alzheimer's disease by interacting with APOE ε4

Some studies have demonstrated interactions of AD-risk single nucleotide polymorphisms (SNPs) in non-APOE regions with APOE genotype. Nevertheless, no study reported interactions of expression quantitative trait locus (eQTL) for APOE with APOE genotype. In present study, we included 9286 unrelated AD patients and 8479 normal controls from 12 cohorts of NIA Genetics of Alzheimer's Disease Data Storage Site (NIAGADS) and Alzheimer's Disease Neuroimaging Initiative (ADNI). 34 unrelated brain eQTLs for APOE were compiled from BRAINEAC and GTEx. We used multi-covariate logistic regression analysis to identify eQTLs interacted with APOE epsilon 4. Adjusted for age and gender, substantia nigra eQTL rs438811 for APOE showed significantly strong interaction with APOE epsilon 4 status (OR, 1.448; CI, 1.124-1.430; P-value = 7.94 x 10(-6)). APOE epsilon 4-based sub-group analyses revealed that carrying one minor allele T of rs438811 can increase the opportunity of developing to AD by 26.75% in APOE epsilon 4 carriers but not in non-carriers. We revealed substantia nigra eQTL rs438811 for APOE can interact with APOE epsilon 4 and confers risk in APOE epsilon 4 carriers only.