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Polygenic risk score for Alzheimer's disease and trajectories of cardiometabolic risk factors in children

By Roxanna S Korologou-Linden, Linda O’Keeffe, Laura D Howe, George Davey Smith, Hannah Jones, Emma L Anderson, Evie Stergiakouli

Posted 28 Mar 2019
bioRxiv DOI: 10.1101/580548 (published DOI: 10.12688/wellcomeopenres.15359.1)

INTRODUCTION: Cardiometabolic factors are implicated in the aetiology of Alzheimer's disease and may lie on the pathways linking genetic variants to Alzheimer's disease across the lifecourse. We examined whether polygenic risk scores (PRS) were associated with cardiometabolic health indicators through childhood and adolescence. METHODS: In 7,977 participants from the Avon Longitudinal Study of Parents and Children, we tested whether a PRS for Alzheimer's disease was associated with trajectories of cardiometabolic risk factors. We examined trajectories for height 1-18 years; lean and fat mass 9-18 years; systolic and diastolic blood pressure 7-18 years; glucose and C-reactive protein 9-18 years; insulin 10-18 years; high and low-density lipoproteins and triglycerides birth-18 years. We also examined birthweight, interleukin-6 (IL-6) at age 9 years and physical activity at ages 11, 12, and 15 years. RESULTS: No consistent associations were observed between the PRS excluding genetic variants in the apolipoprotein E (ApoE) gene region and cardiometabolic factors trajectories across childhood and adolescence. CONCLUSION: We did not detect evidence to suggest that the PRS for Alzheimer's disease acts through childhood and adolescent cardiometabolic risk factors. Further studies should examine whether these associations emerge later in adulthood when variation in cardiometabolic risk factors is likely to be greater.

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