Associations of Genetic Susceptibility to Alzheimer’s Disease with Adiposity and Cardiometabolic Risk Factors among Children in a 2-Year Follow-up Study

Abstract

We investigated the associations of genetic risk score (GRS) for Alzheimer’s disease and apolipoprotein E (APOE) ɛ variant with cardiometabolic risk factors during 2-year follow-up in children and whether body fat percentage (BF%) modify these associations. A population-based sample of 469 children (246 boys, 223 girls) at baseline and 398 children (201 boys, 197 girls) at 2-year follow-up participated in the study. Genotyping was performed using the Illumina Custom Infinium CardioMetabo BeadChip and the Illumina Infinium HumanCoreExome BeadChip. The GRS was calculated using information on nine independent gene variants available in our genomic data. We assessed BF%, waist circumference, insulin, glucose, triglycerides, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, and systolic and diastolic blood pressure. We computed a cardiometabolic risk score and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). In boys, the GRS was not associated with cardiometabolic risk factors. In girls, GRS was directly associated with LDL cholesterol (β= 0.133, 95% CI = 0.002 to 0.262) at baseline and with a higher cardiometabolic risk score (β= 0.154, 95% CI = 0.015 to 0.294), glucose (β= 0.143, 95% CI = 0.003 to 0.284), and HOMA-IR (β= 0.141, 95% CI = 0.004 to 0.278) at 2-year follow-up. GRS was directly associated with a cardiometabolic risk score at baseline and 2-year follow-up among girls in the highest third of BF% at baseline, but not in other girls (p < 0.05 for interaction). Children with the APOE ɛ3/3 genotype had higher LDL cholesterol at and 2-year follow-up than those with the APOE ɛ2/3 genotype. In conclusion, GRS was associated with increased cardiometabolic risk in girls and especially those with higher BF%.