title: Hippocampal transcriptome-guided genetic analysis of correlated episodic memory phenotypes in Alzheimer's disease.
abstract: As the most common type of dementia, Alzheimer's disease (AD) is a neurodegenerative disorder initially manifested by impaired memory performances. While the diagnosis information indicates a dichotomous status of a patient, memory scores have the potential to capture the continuous nature of the disease progression and may provide more insights into the underlying mechanism. In this work, we performed a targeted genetic study of memory scores on an AD cohort to identify the associations between a set of genes highly expressed in the hippocampal region and seven cognitive scores related to episodic memory. Both main effects and interaction effects of the targeted genetic markers on these correlated memory scores were examined. In addition to well-known AD genetic markers APOE and TOMM40, our analysis identified a new risk gene NAV2 through the gene-level main effect analysis. NAV2 was found to be significantly and consistently associated with all seven episodic memory scores. Genetic interaction analysis also yielded a few promising hits warranting further investigation, especially for the RAVLT list B Score.
authors: BioHealth, Indiana University School of Informatics and Computing Indianapolis, IN, USA ; Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine Indianapolis, IN, USA.
authors: Jingwen
authors: J
authors: Yan
authors: Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine Indianapolis, IN, USA ; Indiana Alzheimer Disease Center, Indiana University School of Medicine Indianapolis, IN, USA.
authors: Sungeun
authors: S
authors: Kim
authors: Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine Indianapolis, IN, USA ; Indiana Alzheimer Disease Center, Indiana University School of Medicine Indianapolis, IN, USA.
authors: Kwangsik
authors: K
authors: Nho
authors: Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine Indianapolis, IN, USA ; Computer Science, Dartmouth College Hanover, NH, USA.
authors: Rui
authors: R
authors: Chen
authors: Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine Indianapolis, IN, USA ; Indiana Alzheimer Disease Center, Indiana University School of Medicine Indianapolis, IN, USA.
authors: Shannon L
authors: SL
authors: Risacher
authors: Genetics, Community and Family Medicine, Geisel School of Medicine at Dartmouth Lebanon, NH, USA.
authors: Jason H
authors: JH
authors: Moore
authors: Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine Indianapolis, IN, USA ; Indiana Alzheimer Disease Center, Indiana University School of Medicine Indianapolis, IN, USA ; Medical and Molecular Genetics, Indiana University School of Medicine Indianapolis, IN, USA.
authors: Andrew J
authors: AJ
authors: Saykin
authors: BioHealth, Indiana University School of Informatics and Computing Indianapolis, IN, USA ; Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine Indianapolis, IN, USA ; Indiana Alzheimer Disease Center, Indiana University School of Medicine Indianapolis, IN, USA ; Center for Computational Biology and Bioinformatics, Indiana University School of Medicine Indianapolis, IN, USA.
authors: Li
authors: L
authors: Shen
keywords: Alzheimer's disease; correlated phenotypes; episodic memory; genetic associate study; hippocampus