International genome-wide association study consortium identifies novel loci associated with blood pressure in children and adolescents

Abstract

Background: Our aim was to identify genetic variants associated with blood pressure (BP) in childhood and adolescence. Methods and Results: Genome-wide association study data from participating European ancestry cohorts of the Early Genetics and Lifecourse Epidemiology (EAGLE) Consortium was meta-analyzed across 3 epochs; prepuberty (4-7 years), puberty (8-12 years), and postpuberty (13-20 years). Two novel loci were identified as having genome-wide associations with systolic BP across specific age epochs: rs1563894 (ITGA11, located in active H3K27Ac mark and transcription factor chromatin immunoprecipitation and 5'-C-phosphate-G-3' methylation site) during prepuberty (P=2.86×10⁻⁸) and rs872256 during puberty (P=8.67×10⁻⁹). Several single-nucleotide polymorphism clusters were also associated with childhood BP at P<5×10⁻³. Using a P value threshold of <5×10⁻³, we found some overlap in variants across the different age epochs within our study and between several single-nucleotide polymorphisms in any of the 3 epochs and adult BP-related single-nucleotide polymorphisms. Conclusions: Our results suggest that genetic determinants of BP act from childhood, develop over the lifecourse, and show some evidence of age-specific effects.