Transcriptome-wide association studies (TWAS) have identified several genes that are associated with qualitative traits. In this work, we performed TWAS using quantitative traits and predicted gene expressions in six brain subcortical structures in 286 mild cognitive impairment (MCI) samples from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. The six brain subcortical structures were in the limbic region, basal ganglia region, and cerebellum region. We identified 9, 15, and 6 genes that were stably correlated longitudinally with quantitative traits in these three regions, of which 3, 8, and 6 genes have not been reported in previous Alzheimer's disease (AD) or MCI studies. These genes are potential drug targets for the treatment of early-stage AD. Single-Nucleotide Polymorphism (SNP) analysis results indicated that cis-expression Quantitative Trait Loci (cis-eQTL) SNPs with gene expression predictive abilities may affect the expression of their corresponding genes by specific binding to transcription factors or by modulating promoter and enhancer activities. Further, baseline structure volumes and cis-eQTL SNPs from correlated genes in each region were used to predict the conversion risk of MCI patients. Our results showed that limbic volumes and cis-eQTL SNPs of correlated genes in the limbic region have effective predictive abilities.
Keywords: conversion; longitudinal stably correlated; mild cognitive impairment; quantitative trait; subcortical structure.