Multivariate association between single-nucleotide polymorphisms in Alzgene linkage regions and structural changes in the brain: discovery, refinement and validation.
Stat Appl Genet Mol Biol
; 16(5-6): 349-365, 2017 11 27.
Article
en En
| MEDLINE
| ID: mdl-29091582
ABSTRACT
Using publicly-available data from the Alzheimer's Disease Neuroimaging Initiative, we investigate the joint association between single-nucleotide polymorphisms (SNPs) in previously established linkage regions for Alzheimer's disease (AD) and rates of decline in brain structure. In an initial, discovery stage of analysis, we applied a weighted RV test to assess the association between 75,845 SNPs in the Alzgene linkage regions and rates of change in structural MRI measurements for 56 brain regions affected by AD, in 632 subjects. After confirming association, we selected refined lists of 1694 and 22 SNPs via a bootstrap-enhanced sparse canonical correlation analysis. In a final, validation stage, we confirmed association between the refined list of 1694 SNPs and the imaging phenotypes in an independent data set. Genes corresponding to priority SNPs having the highest contribution in the validation data have previously been implicated or hypothesized to be implicated in AD, including GCLC, IDE, and STAMBP1andFAS. Though the effect sizes of the 1694 SNPs in the priority set are likely small, further investigation within this set may advance understanding of the missing heritability in AD. Our analysis addresses challenges in current imaging-genetics studies such as biased sampling designs and high-dimensional data with low association signal.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Encéfalo
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Análisis Multivariante
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Polimorfismo de Nucleótido Simple
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Ligamiento Genético
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Año:
2017
Tipo del documento:
Article