Literature DB >> 25670335

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

Ganesh Chauhan1, Hieab H H Adams2, Joshua C Bis3, Galit Weinstein4, Lei Yu5, Anna Maria Töglhofer6, Albert Vernon Smith7, Sven J van der Lee8, Rebecca F Gottesman9, Russell Thomson10, Jing Wang11, Qiong Yang11, Wiro J Niessen12, Oscar L Lopez13, James T Becker14, Thanh G Phan15, Richard J Beare16, Konstantinos Arfanakis17, Debra Fleischman18, Meike W Vernooij2, Bernard Mazoyer19, Helena Schmidt6, Velandai Srikanth20, David S Knopman21, Clifford R Jack22, Philippe Amouyel23, Albert Hofman8, Charles DeCarli24, Christophe Tzourio25, Cornelia M van Duijn26, David A Bennett5, Reinhold Schmidt27, William T Longstreth28, Thomas H Mosley29, Myriam Fornage30, Lenore J Launer31, Sudha Seshadri4, M Arfan Ikram32, Stephanie Debette33.   

Abstract

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.
Copyright © 2015 Elsevier Inc. All rights reserved.

Entities:  

Keywords:  Alzheimer; GWAS; Genetic risk score; Hippocampal volume; MRI-Markers

Mesh：

Substances：

Year:  2015        PMID： 25670335      PMCID： PMC4391343          DOI： 10.1016/j.neurobiolaging.2014.12.028

Source DB:  PubMed          Journal:  Neurobiol Aging        ISSN： 0197-4580            Impact factor:   4.673


  46 in total

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W T Longstreth; Oscar L Lopez; Simon Lovestone; Oliver Martinez; Jean-Luc Martinot; Venkata S Mattay; Colm McDonald; Andrew M McIntosh; Katie L McMahon; Francis J McMahon; Patrizia Mecocci; Ingrid Melle; Andreas Meyer-Lindenberg; Sebastian Mohnke; Grant W Montgomery; Derek W Morris; Thomas H Mosley; Thomas W Mühleisen; Bertram Müller-Myhsok; Michael A Nalls; Matthias Nauck; Thomas E Nichols; Wiro J Niessen; Markus M Nöthen; Lars Nyberg; Kazutaka Ohi; Rene L Olvera; Roel A Ophoff; Massimo Pandolfo; Tomas Paus; Zdenka Pausova; Brenda W J H Penninx; G Bruce Pike; Steven G Potkin; Bruce M Psaty; Simone Reppermund; Marcella Rietschel; Joshua L Roffman; Nina Romanczuk-Seiferth; Jerome I Rotter; Mina Ryten; Ralph L Sacco; Perminder S Sachdev; Andrew J Saykin; Reinhold Schmidt; Peter R Schofield; Sigurdur Sigurdsson; Andy Simmons; Andrew Singleton; Sanjay M Sisodiya; Colin Smith; Jordan W Smoller; Hilkka Soininen; Velandai Srikanth; Vidar M Steen; David J Stott; Jessika E Sussmann; Anbupalam Thalamuthu; 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Journal:  Nat Neurosci       Date:  2016-10-03       Impact factor: 24.884
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