Dataset Information

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.

SUBMITTER: Parmar PG

PROVIDER: S-EPMC5279885 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Publications

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

Parmar Priyakumari Ganesh PG Taal H Rob HR Timpson Nicholas J NJ Thiering Elisabeth E Lehtimäki Terho T Marinelli Marcella M Lind Penelope A PA Howe Laura D LD Verwoert Germaine G Aalto Ville V Uitterlinden Andre G AG Briollais Laurent L Evans Dave M DM Wright Margie J MJ Newnham John P JP Whitfield John B JB Lyytikäinen Leo-Pekka LP Rivadeneira Fernando F Boomsma Dorrett I DI Viikari Jorma J Gillman Matthew W MW St Pourcain Beate B Hottenga Jouke-Jan JJ Montgomery Grant W GW Hofman Albert A Kähönen Mika M Martin Nicholas G NG Tobin Martin D MD Raitakari Ollie O Vioque Jesus J Jaddoe Vincent W V VWV Jarvelin Marjo-Riita MR Beilin Lawrence J LJ Heinrich Joachim J van Duijn Cornelia M CM Pennell Craig E CE Lawlor Debbie A DA Palmer Lyle J LJ

Circulation. Cardiovascular genetics 20160311 3

<h4>Background</h4>Our aim was to identify genetic variants associated with blood pressure (BP) in childhood and adolescence.<h4>Methods and results</h4>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 acr ...[more]

PMID: 26969751

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Project description:Hypertension is a crucial risk factor for developing cardiovascular disease and reducing life expectancy. We aimed to detect DNA methylation (DNAm) variants potentially related to systolic blood pressure (SBP) and diastolic blood pressure (DBP) by conducting epigenome-wide association studies in 60 and 59 Chinese monozygotic twin pairs, respectively. Genome-wide DNA methylation profiling in whole blood of twins was performed using Reduced Representation Bisulfite Sequencing, yielding 551,447 raw CpGs. Association between DNAm of single CpG and blood pressure was tested by applying generalized estimation equation. Differentially methylated regions (DMRs) were identified by comb-P approach. Inference about Causation through Examination of Familial Confounding was utilized to perform the causal inference. Ontology enrichment analysis was performed using Genomic Regions Enrichment of Annotations Tool. Candidate CpGs were quantified using Sequenom MassARRAY platform in a community population. Weighted gene co-expression network analysis (WGCNA) was conducted using gene expression data. The median age of twins was 52 years (95% range 40, 66). For SBP, 31 top CpGs (p < 1 × 10-4) and 8 DMRs were identified, with several DMRs within NFATC1, CADM2, IRX1, COL5A1, and LRAT. For DBP, 43 top CpGs (p < 1 × 10-4) and 12 DMRs were identified, with several DMRs within WNT3A, CNOT10, and DAB2IP. Important pathways, such as Notch signaling pathway, p53 pathway by glucose deprivation, and Wnt signaling pathway, were significantly enriched for SBP and DBP. Causal inference analysis suggested that DNAm at top CpGs within NDE1, MYH11, SRRM1P2, and SMPD4 influenced SBP, while SBP influenced DNAm at CpGs within TNK2. DNAm at top CpGs within WNT3A influenced DBP, while DBP influenced DNAm at CpGs within GNA14. Three CpGs mapped to WNT3A and one CpG mapped to COL5A1 were validated in a community population, with a hypermethylated and hypomethylated direction in hypertension cases, respectively. Gene expression analysis by WGCNA further identified some common genes and enrichment terms. We detect many DNAm variants that may be associated with blood pressure in whole blood, particularly the loci within WNT3A and COL5A1. Our findings provide new clues to the epigenetic modification underlying hypertension pathogenesis.

Dataset Information

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

Background

Methods and results

Conclusions

Publications

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

Similar Datasets

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