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Gene-based GWAS and biological pathway analysis of the resilience of executive functioning.


ABSTRACT: 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?×?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?×?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.

SUBMITTER: Mukherjee S 

PROVIDER: S-EPMC3944472 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Gene-based GWAS and biological pathway analysis of the resilience of executive functioning.

Mukherjee Shubhabrata S   Kim Sungeun S   Ramanan Vijay K VK   Gibbons Laura E LE   Nho Kwangsik K   Glymour M Maria MM   Ertekin-Taner Nilüfer N   Montine Thomas J TJ   Saykin Andrew J AJ   Crane Paul K PK  

Brain imaging and behavior 20140301 1


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 thre  ...[more]

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