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

Author:

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

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.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Genetics(clinical),Cardiology and Cardiovascular Medicine,Genetics

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