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Association of Alzheimer's disease GWAS loci with MRI markers of brain aging


Chauhan, G and Adams, HHH and Bis, JC and Weinstein, G and Yu, L and Toglhofer, AM and Smith, AV and van der Lee, SJ and Gottesman, RF and Thomson, R and Wang, J and Yang, Q and Niessen, WJ and Lopez, OL and Becker, JT and Phan, TG and Beare, RJ and Arfanakis, K and Fleischman, D and Vernooij, MW and Mazoyer, BM and Schmidt, H and Srikanth, V and Knopman, DS and Jack Jr, CR and Amouyel, P and Hofman, A and DeCarli, C and Tzourio, C and van Duijn, CM and Bennett, DA and Schmidt, R and Longstreth, WT and Mosley, TH and Fornage, M and Launer, LJ and Seshadri, S and Ikram, MA and Debette, S, Association of Alzheimer's disease GWAS loci with MRI markers of brain aging, Neurobiology of Aging, 36, (4) pp. 1765.e7-1765.e16. ISSN 0197-4580 (2015) [Refereed Article]

Copyright Statement

Copyright 2015 Elsevier Inc.

DOI: doi:10.1016/j.neurobiolaging.2014.12.028


Whether novel risk variants of Alzheimer's disease (AD) identified through genome-wide association studies also influence magnetic resonance imaging-based intermediate phenotypes of AD in the general population is unclear. We studied association of 24 AD risk loci with intracranial volume, total brain volume, hippocampal volume (HV), white matter hyperintensity burden, and brain infarcts in a meta-analysis of genetic association studies from large population-based samples (N = 8175-11,550). In single-SNP based tests, AD risk allele of APOE (rs2075650) was associated with smaller HV (p = 0.0054) and CD33 (rs3865444) with smaller intracranial volume (p = 0.0058). In gene-based tests, there was associations of HLA-DRB1 with total brain volume (p = 0.0006) and BIN1 with HV (p = 0.00089). A weighted AD genetic risk score was associated with smaller HV (beta  SE = -0.047 0.013, p = 0.00041), even after excluding the APOE locus (p = 0.029). However, only association of AD genetic risk score with HV, including APOE, was significant after multiple testing correction (including number of independent phenotypes tested). These results suggest that novel AD genetic risk variants may contribute to structural brain aging in nondemented older community persons.

Item Details

Item Type:Refereed Article
Keywords:Alzheimer, MRI-Markers, genetic risk score, GWAS, hippocampal volume
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Neurosciences not elsewhere classified
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Thomson, R (Dr Russell Thomson)
UTAS Author:Srikanth, V (Dr Velandai Srikanth)
ID Code:99896
Year Published:2015
Web of Science® Times Cited:59
Deposited By:Menzies Institute for Medical Research
Deposited On:2015-04-16
Last Modified:2017-11-06

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