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

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 at 1-18 years; lean and fat mass at 9-18 years; systolic and diastolic blood pressure at 7-18 years; glucose and C-reactive protein at 9-18 years; insulin at 10-18 years; and high and low-density lipoproteins and triglycerides birth at 18 years. We also examined birthweight and 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 gene region and cardiometabolic factors trajectories across childhood and adolescence. Conclusions: 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.

Keywords: Alzheimer's disease; cardiometabolic; polygenic risk scores; trajectories.

Figure 1.. Mean trajectories of anthropometric measures and mean change in anthropometric measures per 1-SD increase in polygenic risk scores (PRS) from ages 9–18 years in ALSPAC.

( A) Height, ( B) lean mass, and ( C) fat mass. The shaded areas in the left graphs and the bars in the right graphs represent 95% confidence intervals, respectively.

Figure 2.. Mean trajectories of blood pressure measures and mean change in blood pressure measures per 1-SD increase in polygenic risk scores (PRS) from ages 7–18 years in ALSPAC.

( A) Systolic blood pressure and ( B) diastolic blood pressure. The shaded areas in the left graphs and the bars in the right graphs represent 95% confidence intervals, respectively.

Figure 3.. Mean trajectories of blood-based biomarkers and mean change per 1-standard deviation increase in PRS.

( A) Glucose from ages 7–18 years, ( B) triglycerides, ( C) non-high-density lipoprotein-cholesterol (HDL-c), and ( D) HDL-c from ages 0–18 years. ( E) C-reactive protein (CRP) from ages 9–18 years. The shaded areas in the left graphs and the bars in the right graphs represent 95% confidence intervals, respectively.