Khondoker, M;
Newhouse, S;
Westman, E;
Muehlboeck, JS;
Mecocci, P;
Vellas, B;
Tsolaki, M;
... Alzheimer's Disease Neuroimaging Initiative; + view all
(2015)
Linking Genetics of Brain Changes to Alzheimer's Disease: Sparse Whole Genome Association Scan of Regional MRI Volumes in the ADNI and AddNeuroMed Cohorts.
Journal of Alzheimer's Disease
, 45
(3)
pp. 851-864.
10.3233/JAD-142214.
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Abstract
Background: Alzheimer’s disease (AD) is a highly heritable disease, but until recently few replicated genetic markers have been identified. Markers identified so far are likely to account for only a tiny fraction of the heritability of AD and many more genetic risk alleles are thought to be undiscovered. Objective: Identifying genetic markers for AD using combined analysis of genetics and brain imaging data. Methods: Imaging quantitative trait loci (iQTLs) has recently emerged as an interesting research area for linking genetics of brain changes to AD. We consider a genome-wide association scan of 109 brain-wide regional imaging phenotypes to identify genetic susceptibility loci for AD from a combined set of 1,045 subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and the AddNeuroMed studies. We use one-SNP-at-a-time as well as multi-SNP Hyperlasso based iQTL methods for the analysis. Results: We identified several novel markers associated with AD, namely HOMER2 (rs1256429; intronic, p = 8.7 × 10 – 10 ), EOMES (rs2724509; flanking), JAM2 (rs2829841; intronic), and WEE1 (rs10770042; coding). The SNP rs1256429 (HOMER2) was one of the top hits in Hyperlasso as well as in the single-SNP analysis showing an association with the volume of the right thalamus and AD, a brain region reported to be linked with AD in several studies. Conclusion: We believe that the markers identified in this study are novel additions to the existing list of genetic variants associated with AD which can be validated in future replicated studies
| Type: | Article |
|---|---|
| Title: | Linking Genetics of Brain Changes to Alzheimer's Disease: Sparse Whole Genome Association Scan of Regional MRI Volumes in the ADNI and AddNeuroMed Cohorts |
| Location: | Netherlands |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3233/JAD-142214 |
| Publisher version: | http://dx.doi.org/10.3233/JAD-142214 |
| Language: | English |
| Additional information: | 2015 – IOS Press and the authors. All rights reserved This article is published online with Open Access and distributed under the terms of the Creative Commons Attribution Non-Commercial License. https://creativecommons.org/licenses/by-nc/3.0/ |
| Keywords: | Alzheimer's disease, genome wide association study, imaging quantitative trait loci, magnetic resonance imaging, mild cognitive impairment |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics > Clinical Epidemiology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1468840 |
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