Effects of HLA-DRB1/DQB1 Genetic Variants on Neuroimaging in Healthy, Mild Cognitive Impairment, and Alzheimer's Disease Cohorts

Alzheimer's disease (AD) is the most common form of dementia and exhibits a considerable level of heritability. Previous association studies gave evidence for the associations of HLA-DRB1/DQB1 alleles with AD. However, how and when the gene variants in HLA-DRB1/DQB1 function in AD pathogenesis has yet to be determined. Here, we firstly investigated the association of gene variants in HLA-DRB1/DQB1 alleles and AD related brain structure on magnetic resonance imaging (MRI) in a large sample from the Alzheimer's Disease Neuroimaging Initiative (ADNI). We selected hippocampus, subregion, parahippocampus, posterior cingulate, precuneus, middle temporal, entorhinal cortex, and amygdala as regions of interest (ROIs). Twelve SNPs in HLA-DRB1/DQB1 were identified in the dataset following quality control measures. In the total group hybrid population analysis, our study (rs35445101, rs1130399, and rs28746809) were associated with the smaller baseline volume of the left posterior cingulate and rs2854275 was associated with the larger baseline volume of the left posterior cingulate. Furthermore, we detected the above four associations in mild cognitive impairment (MCI) sub-group analysis, and two risk loci (rs35445101 and rs1130399) were also the smaller baseline volume of the left posterior cingulate in (NC) sub-group analysis. Our study suggested that HLA-DRB1/DQB1 gene variants appeared to modulate the alteration of the left posterior cingulate volume, hence modulating the susceptibility of AD.