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

Shubhabrata Mukherjee, Sungeun Kim, Vijay K. Ramanan, Laura E. Gibbons, Kwangsik Nho, M. Maria Glymour, Nilüfer Ertekin-Taner, Thomas J. Montine, Andrew Saykin, Paul K. Crane

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)110-118
Number of pages9
JournalBrain Imaging and Behavior
Volume8
Issue number1
DOIs
StatePublished - 2014

Fingerprint

Genome-Wide Association Study
Single Nucleotide Polymorphism
Genes
Genome
Post-Synaptic Density
Dendritic Spines
Neuropsychological Tests
Phenotype
Neurons
Membranes
Brain
Research

Keywords

  • Alzheimer's disease
  • Executive functioning
  • Genes
  • Memory
  • Pathways
  • Resilience

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Neurology
  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience
  • Behavioral Neuroscience
  • Radiology Nuclear Medicine and imaging

Cite this

Mukherjee, S., Kim, S., Ramanan, V. K., Gibbons, L. E., Nho, K., Glymour, M. M., ... Crane, P. K. (2014). Gene-based GWAS and biological pathway analysis of the resilience of executive functioning. Brain Imaging and Behavior, 8(1), 110-118. https://doi.org/10.1007/s11682-013-9259-7

Gene-based GWAS and biological pathway analysis of the resilience of executive functioning. / Mukherjee, Shubhabrata; Kim, Sungeun; Ramanan, Vijay K.; Gibbons, Laura E.; Nho, Kwangsik; Glymour, M. Maria; Ertekin-Taner, Nilüfer; Montine, Thomas J.; Saykin, Andrew; Crane, Paul K.

In: Brain Imaging and Behavior, Vol. 8, No. 1, 2014, p. 110-118.

Research output: Contribution to journalArticle

Mukherjee, S, Kim, S, Ramanan, VK, Gibbons, LE, Nho, K, Glymour, MM, Ertekin-Taner, N, Montine, TJ, Saykin, A & Crane, PK 2014, 'Gene-based GWAS and biological pathway analysis of the resilience of executive functioning', Brain Imaging and Behavior, vol. 8, no. 1, pp. 110-118. https://doi.org/10.1007/s11682-013-9259-7
Mukherjee, Shubhabrata ; Kim, Sungeun ; Ramanan, Vijay K. ; Gibbons, Laura E. ; Nho, Kwangsik ; Glymour, M. Maria ; Ertekin-Taner, Nilüfer ; Montine, Thomas J. ; Saykin, Andrew ; Crane, Paul K. / Gene-based GWAS and biological pathway analysis of the resilience of executive functioning. In: Brain Imaging and Behavior. 2014 ; Vol. 8, No. 1. pp. 110-118.
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