TY  - JOUR
SP  - 851
VL  - 45
N1  - 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/
IS  - 3
SN  - 1387-2877
UR  - http://dx.doi.org/10.3233/JAD-142214
A1  - Khondoker, M
A1  - Newhouse, S
A1  - Westman, E
A1  - Muehlboeck, JS
A1  - Mecocci, P
A1  - Vellas, B
A1  - Tsolaki, M
A1  - K?oszewska, I
A1  - Soininen, H
A1  - Lovestone, S
A1  - Dobson, R
A1  - Simmons, A
A1  - AddNeuroMed consortium
A1  - Alzheimer's Disease Neuroimaging Initiative
JF  - Journal of Alzheimer's Disease
EP  - 864
AV  - public
Y1  - 2015///
TI  - Linking Genetics of Brain Changes to Alzheimer's Disease: Sparse Whole Genome Association Scan of Regional MRI Volumes in the ADNI and AddNeuroMed Cohorts
ID  - discovery1468840
N2  - 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
KW  - Alzheimer's disease
KW  -  genome wide association study
KW  -  imaging quantitative trait loci
KW  -  magnetic resonance imaging
KW  -  mild cognitive impairment
ER  -