Abstract
To identify genetic variants influencing cortical atrophy in Alzheimer's disease (AD), we performed genome-wide association studies (GWAS) of mean cortical thicknesses in 17 AD-related brain. In this study, we used neuroimaging and genetic data of 919 participants from the Alzheimer's Disease Neuroimaging Initiative cohort, which include 268 cognitively normal controls, 488 mild cognitive impairment, 163 AD individuals. We performed GWAS with 3,041,429 single nucleotide polymorphisms (SNPs) for cortical thickness. The results of GWAS indicated that rs10109716 in ST18 (ST18 C2H2C-type zinc finger transcription factor) and rs661526 in NFIA (nuclear factor I A) genes are significantly associated with mean cortical thicknesses of the left inferior frontal gyrus and left parahippocampal gyrus, respectively. The rs661526 regulates the expression levels of NFIA in the substantia nigra and frontal cortex and rs10109716 regulates the expression levels of ST18 in the thalamus. These results suggest a crucial role of identified genes for cortical atrophy and could provide further insights into the genetic basis of AD.
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