Polygenic risk scores for Alzheimer’s disease, and academic achievement, cognitive and behavioural measures in children from the general population
Year: 2019
Type: article
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.
DOI: 10.1093/ije/dyz080
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,514
Awards: G1605161196, National Alzheimer's Coordinating Center, The Avon Longitudinal Study of Parents and Children (ALSPAC): A multi- generation, longitudinal resource focusing on life course health and well- being., Alzheimer's Disease Genetics Consortium, G5470336846, Life course aetiology of dementia and cognitive decline: improving causal inference, CHARGE consortium: omics discovery for CVD and aging phenotypes, A Powerful, Genome-Wide Association Scan for Susceptibility Genes for late-onset Alzheimer's disease, G6689231961, Mendelian randomization to hypothesis-free causal inference, G7448564355, Mediation analysis in life course epidemiology: methodological innovation and application to studies of obesity and cardiometabolic health, G7990456425, G801210579, G8393905554, AD Gene Discovery: Exome Chip, New Endophenotypes & Functional Studies in CHARGE, National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)
OpenAlex ID: W2944473045