School of Psychology, University of Galway, Galway, Ireland.
Centre for Neuroimaging, Cognition & Genomics, University of Galway, Galway, Ireland.
Genes Brain Behav. 2023 Aug;22(4):e12850. doi: 10.1111/gbb.12850. Epub 2023 Jul 4.
Cognitive ability is a strong predictor of occupational achievement, quality of life and physical health. While variation in cognition is strongly heritable and has been robustly associated with early environment and brain morphology, little is known about how these factors combine and interact to explain this variation in cognition. To address this, we modelled the relationship between common genetic variation, grey matter volume, early life adversity and education and cognitive ability in a UK Biobank sample of N = 5237 individuals using structural equation modelling. We tested the hypotheses that total grey matter volume would mediate the association between genetic variation and cognitive ability, and that early life adversity and educational attainment would moderate this relationship. Common genetic variation, grey matter volume and early life adversity were each significant predictors in the model, explaining 15% of variation in cognitive ability. Contrary to our hypothesis, grey matter volume did not mediate the relation between genetic variation and cognition performance. Neither did early life adversity or educational attainment moderate this relation, although educational attainment was observed to moderate the relationship between grey matter volume and cognitive performance. We interpret these findings in terms of the modest explanatory value of currently estimated polygenic scores accounting for variation in cognitive performance (5%), making potential mediating and moderating variables difficult to confirm.
认知能力是职业成就、生活质量和身体健康的强有力预测指标。虽然认知能力的变化具有很强的遗传性，并且与早期环境和大脑形态学密切相关，但对于这些因素如何结合和相互作用来解释认知能力的变化，我们知之甚少。为了解决这个问题，我们使用结构方程模型，在英国生物库的 5237 名个体样本中，对常见遗传变异、灰质体积、早期生活逆境和教育与认知能力之间的关系进行建模。我们检验了以下假设：总灰质体积将在遗传变异和认知能力之间的关联中起中介作用，而早期生活逆境和教育程度将调节这种关系。常见的遗传变异、灰质体积和早期生活逆境都是模型中的重要预测因子，解释了认知能力约 15%的变异。与我们的假设相反，灰质体积并没有在遗传变异与认知表现之间起中介作用。早期生活逆境或教育程度也没有调节这种关系，尽管观察到教育程度调节了灰质体积与认知表现之间的关系。我们根据目前估计的多基因评分对认知表现变化的解释能力（~5%）来解释这些发现，这些评分解释了认知能力变化的大部分原因，使得潜在的中介和调节变量难以确认。
