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

Circ Cardiovasc Genet. 2016 Jun;9(3):266-278. doi: 10.1161/CIRCGENETICS.115.001190. Epub 2016 Mar 11.

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.

Keywords: Genome-Wide Association Study; blood pressure; children; genetic epidemiology; hypertension; prehypertension.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Multicenter Study

MeSH terms

  • Adolescent
  • Age Factors
  • Blood Pressure / genetics*
  • Child
  • Child, Preschool
  • European Continental Ancestry Group / genetics
  • Female
  • Genetic Loci*
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Hypertension / diagnosis
  • Hypertension / ethnology
  • Hypertension / genetics*
  • Hypertension / physiopathology
  • Integrin alpha Chains / genetics*
  • Male
  • Molecular Epidemiology
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Risk Assessment
  • Risk Factors
  • Young Adult

Substances

  • Genetic Markers
  • ITGA11 protein, human
  • Integrin alpha Chains