Genome-wide association study on longitudinal and cross-sectional traits of child health and development in a Japanese population

Understanding the influence of both genetics and environment on human health, especially early in life, is essential for shaping long-term health. Here, we utilize a nationwide prospective birth cohort, the Japan Environment and Childrens Study (JECS), to conduct a large-scale population-based genetic study using biannual questionnaire surveys and biological and physical measurements collected from both parents and their children since the participant mothers were pregnant. Analyses of genome-wide genotyping for 80,639 child participants with parental consent and sufficient DNA from cord blood samples represent the genetic diversity of the general population in Japan. Systematic genome-wide association studies of 1,148 child health and developmental traits (including, e.g., food allergy, anthropometry measurements or ASQ-3 developmental screening) and parental environmental exposure traits (including, e.g., mercury or PFAS exposure) identify 5,685 common genomic loci (2,218 of which passed the phenome-wide significance threshold = 4.4 x 10-11), of which 15-17% of loci represent novel associations not previously reported, including potential future therapeutic targets. Additional longitudinal GWAS of BMI, using Gaussian process regression, identified 153 novel dynamic genetic associations throughout child development. These associations can also be used to predict an individuals growth trajectory based on their genetic background. In addition, genetic correlation analysis suggested some evidence that maternal environmental exposures during pregnancy influence child traits at birth. Together with studies of genetic risk factors and environmental exposures, across time and multiple outcomes, these demonstrate the uniqueness and value of the JECS data.