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Polygenic predictors of age-related decline in cognitive ability

By Stuart J. Ritchie, W. David Hill, Riccardo E. Marioni, Gail Davies, Saskia P Hagenaars, Sarah E. Harris, Simon R Cox, Adele M. Taylor, Janie Corley, Alison Pattie, Paul Redmond, John M. Starr, Ian J Deary

Posted 24 Jul 2018
bioRxiv DOI: 10.1101/375691 (published DOI: 10.1038/s41380-019-0372-x)

Polygenic scores can be used to distil the knowledge gained in genome-wide association studies for prediction of health, lifestyle, and environmental factors in independent samples. In this preregistered study, we used fourteen polygenic scores to predict variation in cognitive ability level at age 70 and cognitive change from age 70 to age 79 in the longitudinal Lothian Birth Cohort 1936 study. The polygenic scores were created for phenotypes that have been suggested as risk or protective factors for cognitive ageing. Cognitive abilities within old age were indexed using a latent general factor estimated from thirteen varied cognitive tests taken at four waves, each three years apart (initial n = 1,091 age 70; final n = 550 age 79). The general factor indexed over two-thirds of the variance in longitudinal cognitive change. We also ran an additional analysis using an age-11 intelligence test to index cognitive change from age 11 to age 70. Several polygenic scores were associated with the level of cognitive ability at age-70 baseline (range of standardized beta-values = -.178 to .264), and the score for education was associated with cognitive change from childhood to age 70 (standardized beta = .102). None was statistically significantly associated with variation in cognitive change between ages 70 and 79. APOE e4 status made a significant prediction of cognitive decline from age 70 to 79 (standardized beta = -.319 for carriers vs. non-carriers). The results suggest that the predictive validity for cognitive ageing of polygenic scores derived from genome-wide association study summary statistics is not yet on a par with APOE e4, a more well-established predictor.

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