A genome-wide association study of childhood adiposity and blood lipids

Abstract

Background: The rising prevalence of childhood obesity and dyslipidaemia is a major public health concern due to its association with morbidity and mortality in later life. Previous studies have found that genetic variants inherited at birth can begin to exert their effects on cardiometabolic traits during the early stages of the lifecourse. Methods: In this study, we have conducted genome-wide association studies (GWAS) for eight measures of adiposity and lipids in a cohort of young individuals (mean age 9.9 years, sample sizes=4,202 to 5,766) from the Avon Longitudinal Study of Parents and Children (ALSPAC). These measures were body mass index (BMI), systolic and diastolic blood pressure, high- density and low-density lipoprotein cholesterol, triglycerides, apolipoprotein A-I and apolipoprotein B. We next undertook functional enrichment, pathway analyses and linkage disequilibrium (LD) score regression to evaluate genetic correlations with later-life cardiometabolic diseases. Results: Using GWAS we identified 14 unique loci associated with at least one risk factor in this cohort of age 10 individuals (P<5x10-8), with lipoprotein lipid-associated loci being enriched for liver tissue-derived gene expression and lipid synthesis pathways. LD score regression provided evidence of various genetic correlations, such as childhood systolic blood pressure being genetically correlated with later-life coronary artery disease (rG=0.26, 95% CI=0.07 to 0.46, P=0.009) and hypertension (rG=0.37, 95% CI=0.19 to 0.55, P=6.57x10-5), as well as childhood BMI with type 2 diabetes (rG=0.35, 95% CI=0.18 to 0.51, P=3.28x10-5). Conclusions: Our findings suggest that there are genetic variants inherited at birth which begin to exert their effects on cardiometabolic risk factors as early as age 10 in the life course. However, further research is required to assess whether the genetic correlations we have identified are due to direct or indirect effects of childhood adiposity and lipid traits.