International Genome-Wide Association Study Consortium Identifies Novel Loci Associated With Blood Pressure in Children and Adolescents.

Priyakumari Ganesh Parmar, H Rob Taal, Nicholas J Timpson, Elisabeth Thiering, Terho Lehtimäki, Marcella Marinelli, Penelope A Lind, Laura D Howe, Germaine Verwoert, Ville Aalto, Andre G Uitterlinden, Laurent Briollais, Dave M Evans, Margie J Wright, John P Newnham, John B Whitfield, Leo-Pekka Lyytikäinen, Fernando Rivadeneira, Dorrett I Boomsma, Jorma Viikari, Matthew W Gillman, Beate St Pourcain, Jouke-Jan Hottenga, Grant W Montgomery, Albert Hofman, Mika Kähönen, Nicholas G Martin, Martin D Tobin, Ollie Raitakari, Jesus Vioque, Vincent W V Jaddoe, Marjo-Riita Jarvelin, Lawrence J Beilin, Joachim Heinrich, Cornelia M van Duijn, Craig E Pennell, Debbie A Lawlor, Lyle J Palmer

Journal: Circulation. Cardiovascular genetics 2017;9(3):266-278

PMID: 26969751

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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.

DOI: 10.1161/CIRCGENETICS.115.001190

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MeSH Terms: Adolescent, Age Factors, Blood Pressure, Child, Child, Preschool, Female, Genetic Loci, Genetic Markers, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Hypertension, Integrin alpha Chains, Male, Molecular Epidemiology, Phenotype, Polymorphism, Single Nucleotide, Risk Assessment, Risk Factors, White People, Young Adult