Polygenic risk score for Alzheimer’s disease and trajectories of cardiometabolic risk factors in children
Year: 2019
Type: preprint
Abstract: 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 life course. 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.
DOI: 10.1101/580548
Institutions: University of Bristol, MRC Integrative Epidemiology Unit
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funders: Alzheimer's Association, Wellcome Trust, Development of Innovative Strategies for a Transdisciplinary approach to ALZheimer's disease, Université de Lille, British Heart Foundation, University of Bristol, Institut National de la Santé et de la Recherche Médicale, Bundesministerium für Bildung und Forschung, Erasmus Medisch Centrum, Hjartavernd, Centre hospitalier régional universitaire de Lille, National Institutes of Health, Medical Research Council, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: G1108310052, G1173778324, G1182606701, G1192034430, Kompetenznetz 'Demenzen', G1605161196, G1653514516, G1901425420, ALSPAC: consolidation of a two generation cell line backed resource, for the study of the environment and genetic determinants of health and development from before birth to late puberty., G1924190148, G2179969359, G2193588257, G230712557, G2538597952, Understanding gender differences in cardiometabolic risk across the life course, G2697093250, G2929235049, G3161882281, G3214719652, G3233549029, National Alzheimer's Coordinating Center, G3386955339, G3402222819, G346328595, G3831911591, G3915381216, G3916087950, The Avon Longitudinal Study for Parents and Children: An international resource for population genomic and lifecourse epidemiology. Core programme support 2014-2019., G4838234079, Alzheimer's Disease Genetics Consortium, G5470336846, Life course aetiology of dementia and cognitive decline: improving causal inference, Investigation of the influence of habitual level of vigorous physical activity on skeletal strength in late adolescence., G5558075022, G5562631338, CHARGE consortium: omics discovery for CVD and aging phenotypes, A Powerful, Genome-Wide Association Scan for Susceptibility Genes for late-onset Alzheimer's disease, G6285097384, Verbundprojekt: Kompetenznetz Demenzen - Epidemiologie: Teilprojekte der Universität Bonn, G639185302, G6425121803, G6648385527, G6708752960, G6784606187, Mendelian randomization to hypothesis-free causal inference, Maternal overnutrition and offspring fat mass, metabolic and vascular function., G7046104286, Verbundprojekt Kompetenznetz Demenzen: Teilprojekte des ZISG Mannheim (2. Förderphase), G7373387228, G7431531211, G7448564355, G7828794151, Mediation analysis in life course epidemiology: methodological innovation and application to studies of obesity and cardiometabolic health, G7990456425, G8393905554, AD Gene Discovery: Exome Chip, New Endophenotypes & Functional Studies in CHARGE, G8502142660, G8506111834, G8520273129, G863491659, G8951052545, Early Life determinants of Blood pressure patterns in young Adults (ELBA Study)., G9000030076, National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)
OpenAlex ID: W2924637088