OBJECTIVE Several studies report a polygenic component of risk for Alzheimer's disease. Understanding whether this polygenic signal is associated with educational, cognitive and behavioural outcomes in children could provide an earlier window for intervention. METHODS We examined whether polygenic risk scores (PRS) at varying P-value thresholds in children from the Avon Longitudinal Study of Parents and Children were associated with academic achievement, cognitive and behavioural measures in childhood and adolescence. RESULTS We did not detect any evidence that the genome-wide significant PRS (5x10-8) were associated with these outcomes. PRS at the highest P-value threshold examined (P ≤ 5x10-1) were associated with lower academic achievement in adolescents (Key Stage 3; β: -0.03; 95% confidence interval: -0.05, -0.003) but the effect was attenuated when single nucleotide polymorphisms (SNPs) associated with educational attainment were removed. These PRS were associated with lower IQ (β: -0.04; 95% CI: -0.07, -0.02) at age 8 years with the effect remaining after removing SNPs associated with educational attainment. CONCLUSIONS SNPs mediating the biological effects of Alzheimer's disease are unlikely to operate early in life. The evidence of association between PRS for Alzheimer's disease at liberal thresholds and cognitive measures suggest shared genetic pathways between Alzheimer's disease, academic achievement and cognition.

中文翻译：

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阿尔茨海默病的多基因风险评分以及普通人群儿童的学业成绩、认知和行为测量。

目的 多项研究报告了阿尔茨海默病风险的多基因成分。了解这种多基因信号是否与儿童的教育、认知和行为结果相关，可以为干预提供更早的窗口。方法 我们检查了雅芳父母和儿童纵向研究中儿童在不同 P 值阈值下的多基因风险评分 (PRS) 是否与儿童和青春期的学业成绩、认知和行为测量相关。结果我们没有发现任何证据表明全基因组显着 PRS (5x10-8) 与这些结果相关。所检查的最高 P 值阈值 (P ≤ 5x10-1) 的 PRS 与青少年较低的学业成绩相关（关键阶段 3；β：-0.03；95% 置信区间：-0.05，-0.003），但效果减弱当与教育程度相关的单核苷酸多态性（SNP）被删除时。这些 PRS 与 8 岁时的较低智商相关（β：-0.04；95% CI：-0.07，-0.02），在去除与教育程度相关的 SNP 后，这种影响仍然存在。结论 介导阿尔茨海默病生物学效应的 SNP 不太可能在生命早期发挥作用。自由阈值下的阿尔茨海默病 PRS 与认知测量之间存在关联的证据表明，阿尔茨海默病、学业成就和认知之间存在共同的遗传途径。