Genome-wide transcriptome analysis identifies novel dysregulated genes implicated in Alzheimer's pathology
- Nho, Kwangsik
- Nudelman, Kelly
- Allen, Mariet
- Hodges, Angela
- Kim, Sungeun
- Risacher, Shannon L.
- Apostolova, Liana G.
- Lin, Kuang
- Lunnon, Katie
- Wang, Xue
- Burgess, Jeremy D.
- Ertekin-Taner, Nilüfer
- Petersen, Ronald C.
- Wang, Lisu
- Qi, Zhenhao
- He, Aiqing
- Neuhaus, Isaac
- Patel, Vishal
- Foroud, Tatiana
- Faber, Kelley M.
- Lovestone, Simon
- Simmons, Andrew
- Weiner, Michael W.
- Saykin, Andrew J.
DOIAbstract
INTRODUCTION: Abnormal gene expression patterns may contribute to the onset and progression of late-onset Alzheimer’s disease (LOAD). METHODS: We performed transcriptome-wide meta-analysis (N=1,440) of blood-based microarray gene expression profiles as well as neuroimaging and CSF endophenotype analysis. RESULTS: We identified and replicated five genes (CREB5, CD46, TMBIM6, IRAK3, and RPAIN) as significantly dysregulated in LOAD. The most significantly altered gene, CREB5, was also associated with brain atrophy and increased amyloid-β accumulation, especially in the entorhinal cortex region. cis-eQTL mapping analysis of CREB5 detected five significant associations (p<5x10−8), where rs56388170 (most significant) was also significant...
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