Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Dec 1;48(6):1972-1980.
doi: 10.1093/ije/dyz080.

Polygenic risk scores for Alzheimer's disease, and academic achievement, cognitive and behavioural measures in children from the general population

Affiliations

Polygenic risk scores for Alzheimer's disease, and academic achievement, cognitive and behavioural measures in children from the general population

Roxanna Korologou-Linden et al. Int J Epidemiol. .

Abstract

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.

Keywords: ALSPAC; Alzheimer’s disease; behavioural; cognitive; polygenic risk scores.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Potential mechanisms of associations between PRS for Alzheimer’s disease and cognitive ability/academic achievement. Please note that these are not intended to be directed acyclic graphs. AD denotes Alzheimer’s disease. In panel (a), genetic variants for Alzheimer’s disease cause Alzheimer’s disease protopathology, which manifests as lower IQ and poorer academic achievement at young ages. This could result in reduced ability to tolerate and compensate for Alzheimer’s disease pathology. Panel (b) describes the situation where genetic variants that increase predisposition for Alzheimer’s disease affect academic achievement and/or cognitive ability through an independent pathway (horizontal pleiotropy). In panel (c), genetic variants used to instrument Alzheimer’s disease have their primary effect on Alzheimer’s disease through academic achievement and/or cognitive ability rather than vice versa.

References

    1. Alzheimer’s Association. 2015 Alzheimer’s disease facts and figures. Alzheimers Dement 2015;11:332–84. - PubMed
    1. Geda YE, Knopman DS, Mrazek DA. et al. Depression, apolipoprotein E genotype, and the incidence of mild cognitive impairment: a prospective cohort study. Arch Neurol 2006;63:435–40. - PubMed
    1. Gallagher D, Coen R, Kilroy D. et al. Anxiety and behavioural disturbance as markers of prodromal Alzheimer’s disease in patients with mild cognitive impairment. Int J Geriatr Psychiatry 2011;26:166–72. - PubMed
    1. Mayeux R, Stern Y.. Epidemiology of Alzheimer disease. Cold Spring Harb Perspect Med 2012;2. doi: 10.1101/cshperspect.a006239. - PMC - PubMed
    1. Lambert JC, Ibrahim-Verbaas CA, Harold D. et al. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease. Nat Genet 2013;45:1452–58. - PMC - PubMed

Publication types