Genome-wide association study on longitudinal and cross-sectional traits of child health and development in a Japanese population
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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 Children's 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 80,638 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 1,163 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 4,985 common genomic loci (of which 1,885 loci passed the phenome-wide significant P=4.3 x 10^(-11)), of which 25% of loci represent novel associations not previously reported. Additional longitudinal GWAS of BMI using Gaussian process regression identified 66 novel dynamic genetic associations along child development. In addition, genetic correlation analysis suggested some evidence that maternal environmental exposures during pregnancy influence child traits at birth. Together with studies of environmental exposures and genetic risk factors, across time and multiple outcomes, these demonstrate the uniqueness and value of the JECS data.
