Department of Medicine, University of Washington, Box 359780, 325 Ninth Avenue, Seattle, WA, 98104, USA,
Brain Imaging Behav. 2014 Mar;8(1):110-8. doi: 10.1007/s11682-013-9259-7.
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.
执行功能（EF）的弹性表现为神经心理学测试表现测量的 EF 较高，尽管存在神经退行性疾病引起的结构性脑损伤。我们之前报告了 EF 弹性的单核苷酸多态性（SNP）全基因组关联研究（GWAS）结果。在这里，我们报告了针对同一弹性表型的基于基因和途径的分析，使用最佳 SNP 集（序列）核关联测试（SKAT）进行基因分析（全基因组显著性的保守阈值= 0.05/18,123 = 2.8×10(-6)) 和基因集富集包 GSA-SNP 进行生物途径分析（错误发现率 (FDR) < 0.05）。基因分析发现 RNASE13 与 EF 弹性之间存在全基因组显著关联（p=1.33×10(-7))。与树突/神经元棘、突触前膜、突触后密度等相关的遗传途径与 EF 弹性相关。尽管有必要对这些结果进行复制，但我们的发现表明基于基因和途径的分析在研究认知弹性决定因素方面具有潜在价值。
