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

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; ?: -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 (?: -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.

SUBMITTER: Korologou-Linden R

PROVIDER: S-EPMC6929531 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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

Korologou-Linden Roxanna R Anderson Emma L EL Jones Hannah J HJ Davey Smith George G Howe Laura D LD Stergiakouli Evie E

International journal of epidemiology 20191201 6

<h4>Objective</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 31056667

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Project description:Objective:Genome-wide association studies (GWAS) have identified over 30 susceptibility loci associated with Alzheimer's disease (AD). Using AD GWAS data from the International Genomics of Alzheimer's Project (IGAP), Polygenic Risk Score (PRS) was successfully applied to predict life time risk of AD development. A recently introduced Polygenic Hazard Score (PHS) is able to quantify individuals with age-specific genetic risk for AD. The aim of this study was to quantify the age-specific genetic risk for AD with PRS and compare the results generated by PRS with those from PHS. Methods:Quantification of individual differences in age-specific genetic risk for AD identified by the PRS, was performed with Cox Regression on 9903 (2626 cases and 7277 controls) individuals from the Genetic and Environmental Risk in Alzheimer's Disease consortium (GERAD). Polygenic Hazard Scores were generated for the same individuals. The age-specific genetic risk for AD identified by the PRS was compared with that generated by the PHS. This was repeated using varying SNPs P-value thresholds for disease association. Results:Polygenic Risk Score significantly predicted the risk associated with age at AD onset when SNPs were preselected for association to AD at P ? 0.001. The strongest effect (B = 0.28, SE = 0.04, P = 2.5 × 10-12) was observed for PRS based upon genome-wide significant SNPs (P ? 5 × 10-8). The strength of association was weaker with less stringent SNP selection thresholds. Interpretation:Both PRS and PHS can be used to predict an age-specific risk for developing AD. The PHS approach uses SNP effect sizes derived with the Cox Proportional Hazard Regression model. When SNPs were selected based upon AD GWAS case/control P ? 10-3, we found no advantage of using SNP effects sizes calculated with the Cox Proportional Hazard Regression model in our study. When SNPs are selected for association with AD risk at P > 10-3, the age-specific risk prediction results are not significant for either PRS or PHS. However PHS could be more advantageous than PRS of age specific AD risk predictions when SNPs are prioritized for association with AD age at onset (i.e., powerful Cox Regression GWAS study).

Dataset Information

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

Publications

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

Similar Datasets

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