Background

Deficits in executive functions (EFs), cognitive processes that control goal-directed behaviors, are associated with psychopathology and neurologic disorders. Little is known about the molecular bases of individual differences in EFs. Prior candidate gene studies have been underpowered in their search for dopaminergic processes involved in cognitive functioning, and existing genome-wide association studies of EFs used small sample sizes and/or focused on individual tasks that are imprecise measures of EFs.

Methods

We conducted a genome-wide association study of a common EF (cEF) factor score based on multiple tasks in the UK Biobank (n = 427,037 individuals of European descent).

Results

We found 129 independent genome-wide significant lead variants in 112 distinct loci. cEF was associated with fast synaptic transmission processes (synaptic, potassium channel, and GABA [gamma-aminobutyric acid] pathways) in gene-based analyses. cEF was genetically correlated with measures of intelligence (IQ) and cognitive processing speed, but cEF and IQ showed differential genetic associations with psychiatric disorders and educational attainment.

Conclusions

Results suggest that cEF is a genetically distinct cognitive construct that is particularly relevant to understanding the genetic variance in psychiatric disorders.

中文翻译：

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全基因组关联研究表明，执行功能受到 GABA 能过程的影响，并且是精神疾病的神经认知遗传相关性

 背景

执行功能（EF）的缺陷，即控制目标导向行为的认知过程，与精神病理学和神经系统疾病有关。对于 EF 个体差异的分子基础知之甚少。先前的候选基因研究在寻找与认知功能有关的多巴胺能过程方面动力不足，并且现有的 EF 的全基因组关联研究使用小样本量和/或侧重于对 EF 不精确测量的个体任务。

 方法

我们基于英国生物银行的多项任务（ n = 427,037 名欧洲血统个体）对常见 EF (cEF) 因子评分进行了全基因组关联研究。

 结果

我们在 112 个不同基因座中发现了 129 个独立的全基因组显着先导变异。在基于基因的分析中，cEF 与快速突触传递过程（突触、钾通道和 GABA [γ-氨基丁酸] 途径）相关。 cEF 与智力 (IQ) 和认知处理速度的测量具有遗传相关性，但 cEF 和 IQ 显示出与精神疾病和教育程度的不同遗传关联。

 结论

结果表明，cEF 是一种遗传上独特的认知结构，与理解精神疾病的遗传变异特别相关。