Fine-mapping the effects of Alzheimer's disease risk loci on brain morphology

Journal article (2016)

Authors

Gennady Roshchupkin Erasmus Medical Centre
G. Roshchupkin Erasmus Medical Centre
G. V. Roshchupkin Erasmus Medical Centre
Gennady V. Roshchupkin Erasmus Medical Centre
H. H H Adams Erasmus Medical Centre
Hieab H H Adams Erasmus Medical Centre
H Adams Erasmus Medical Centre
Hieab H. Adams Erasmus Medical Centre
Sven J. Van Der Lee Erasmus Medical Centre
Sven J. van der Lee Erasmus Medical Centre
Meike W. Vernooij Erasmus Medical Centre
M. W. Vernooij Erasmus Medical Centre
C. M. Van Duijn Erasmus Medical Centre
Cornelia M. Van Duijn Erasmus Medical Centre
Cornelia M. van Duijn Erasmus Medical Centre
C. M. van Duijn Erasmus Medical Centre
André G. Uitterlinden Erasmus Medical Centre
Andre G. Uitterlinden Erasmus Medical Centre
Aad van Der Lugt Erasmus Medical Centre
Aad Van der Lugt Erasmus Medical Centre
Aad van der Lugt Erasmus Medical Centre
A. Van der Lugt Erasmus Medical Centre
A. van der Lugt Erasmus Medical Centre
Aad Van Der Lugt Erasmus Medical Centre
A. Van Der Lugt Erasmus Medical Centre
A. van Der Lugt Erasmus Medical Centre
A Hofman Erasmus Medical Centre
Albert Hofman Erasmus Medical Centre
A. Hofman Erasmus Medical Centre
Wiro Niessen Erasmus Medical Centre, ImPhys/Quantitative Imaging
W. J. Niessen Erasmus Medical Centre, ImPhys/Quantitative Imaging
Wiro J. Niessen Erasmus Medical Centre, ImPhys/Quantitative Imaging
WJ Niessen Erasmus Medical Centre, ImPhys/Quantitative Imaging
W.J. Niessen Erasmus Medical Centre, ImPhys/Quantitative Imaging
Wiro J.N. Niessen Erasmus Medical Centre, ImPhys/Quantitative Imaging
M. A. Ikram Erasmus Medical Centre
M. Arfan Ikram Erasmus Medical Centre
Mohammad A. Ikram Erasmus Medical Centre
Research Group
ImPhys/Quantitative Imaging
More Info
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Published Date

01-12-2016

Language

English

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Research Group

ImPhys/Quantitative Imaging

Abstract

The neural substrate of genetic risk variants for Alzheimer's disease (AD) remains unknown. We studied their effect on healthy brain morphology to provide insight into disease etiology in the preclinical phase. We included 4071 nondemented, elderly participants of the population-based Rotterdam Study who underwent brain magnetic resonance imaging and genotyping. We performed voxel-based morphometry (VBM) on all gray-matter voxels for 19 previously identified, common AD risk variants. Whole-brain expression data from the Allen Human Brain Atlas was used to examine spatial overlap between VBM association results and expression of genes in AD risk loci regions. Brain regions most significantly associated with AD risk variants were the left postcentral gyrus with ABCA7 (rs4147929, p = 4.45 × 10−6), right superior frontal gyrus by ZCWPW1 (rs1476679, p = 5.12 × 10−6), and right postcentral gyrus by APOE (p = 6.91 × 10−6). Although no individual voxel passed multiple-testing correction, we found significant spatial overlap between the effects of AD risk loci on VBM and the expression of genes (MEF2C, CLU, and SLC24A4) in the Allen Brain Atlas. Results are available online on www.imagene.nl/ADSNPs/. In this single largest imaging genetics data set worldwide, we found that AD risk loci affect cortical gray matter in several brain regions known to be involved in AD, as well as regions that have not been implicated before.