期刊
BRAIN IMAGING AND BEHAVIOR
卷 8, 期 1, 页码 110-118出版社
SPRINGER
DOI: 10.1007/s11682-013-9259-7
关键词
Memory; Executive functioning; Alzheimer's disease; Genes; Resilience; Pathways
类别
资金
- Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- Canadian Institutes of Health Research
- NIH [P30 AG010129, K01 AG030514, R01 AG029672, R13 AG030995, P50 AG0513]
- Dana Foundation
- NIA [R01 AG032990, P50 AG016574, R01 AG19771, P30 AG10133]
Resilience in executive functioning (EF) is characterized by high EF measured by neuropsychological test performance despite structural brain damage from neurodegenerative conditions. We previously reported single nucleotide polymorphism (SNP) genome-wide association study (GWAS) results for EF resilience. Here, we report gene- and pathway-based analyses of the same resilience phenotype, using an optimal SNP-set (Sequence) Kernel Association Test (SKAT) for gene-based analyses (conservative threshold for genome-wide significance = 0.05/18,123 = 2.8 x 10(-6)) and the gene-set enrichment package GSA-SNP for biological pathway analyses (False discovery rate (FDR) < 0.05). Gene-based analyses found a genome-wide significant association between RNASE13 and EF resilience (p = 1.33 x 10(-7)). Genetic pathways involved with dendritic/neuron spine, presynaptic membrane, postsynaptic density, etc., were enriched with association to EF resilience. Although replication of these results is necessary, our findings indicate the potential value of gene- and pathway-based analyses in research on determinants of cognitive resilience.
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