International Genome-Wide Association Study Consortium Identifies Novel Loci Associated With Blood Pressure in Children and Adolescents.
Parmar PG., Taal HR., Timpson NJ., Thiering E., Lehtimäki T., Marinelli M., Lind PA., Howe LD., Verwoert G., Aalto V., Uitterlinden AG., Briollais L., Evans DM., Wright MJ., Newnham JP., Whitfield JB., Lyytikäinen L-P., Rivadeneira F., Boomsma DI., Viikari J., Gillman MW., St Pourcain B., Hottenga J-J., Montgomery GW., Hofman A., Kähönen M., Martin NG., Tobin MD., Raitakari O., Vioque J., Jaddoe VWV., Jarvelin M-R., Beilin LJ., Heinrich J., van Duijn CM., Pennell CE., Lawlor DA., Palmer LJ., Early Genetics and Lifecourse Epidemiology Consortium None.
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.