Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.3233/JAD-142214

Type

Journal article

Journal

J Alzheimers Dis

Publication Date

2015

Volume

45

Pages

851 - 864

Keywords

Alzheimer's disease, genome wide association study, imaging quantitative trait loci, magnetic resonance imaging, mild cognitive impairment, Aged, Aged, 80 and over, Alzheimer Disease, Brain, Carrier Proteins, Cell Adhesion Molecules, Cell Cycle Proteins, Cohort Studies, Female, Genetic Association Studies, Homer Scaffolding Proteins, Humans, Magnetic Resonance Imaging, Male, Nuclear Proteins, Polymorphism, Single Nucleotide, Protein-Tyrosine Kinases, Quantitative Trait Loci, Sex Factors, T-Box Domain Proteins