International GWAS 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; André G Uitterlinden; Laurent Briollais; David M Evans; Margaret J Wright; John P Newnham; John B Whitfield; Leo-Pekka Lyytikäinen; Fernando Rivadeneira; Dorret 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; Olli Raitakari; Jesus Vioque; Vincent W V Jaddoe; Marjo-Riitta Jarvelin; Lawrence J Beilin; Joachim Heinrich; Cornelia M van Duijn; Craig E Pennell; Debbie A Lawlor; Lyle J Palmer; EArly Genetics and Lifecourse Epidemiology Consortium

doi:10.1161/CIRCGENETICS.115.001190

International GWAS 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
, André G Uitterlinden
, Laurent Briollais
, David M Evans
, Margaret J Wright
, John P Newnham
, John B Whitfield
, Leo-Pekka Lyytikäinen
, Fernando Rivadeneira
, Dorret 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, Olli Raitakari, Jesus Vioque, Vincent W V Jaddoe, Marjo-Riitta Jarvelin, Lawrence J Beilin, Joachim Heinrich, Cornelia M van Duijn, Craig E Pennell, Debbie A Lawlor, Lyle J Palmer, EArly Genetics and Lifecourse Epidemiology Consortium

Research output: Contribution to journal › Article (Academic Journal) › peer-review

39 Citations (Scopus)

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 EAGLE ( EA: rly G: enetics and L: ifecourse E: pidemiology) Consortium was meta-analysed across three 'epochs'; pre-puberty [4-7 years], puberty [8-12 years] and post-puberty [13-20 years]. Two novel loci were identified as having genome-wide associations with systolic blood pressure across specific age epochs; rs1563894 (ITGA11, located in active H3K27Ac mark and transcription factor CHiP and CpG methylation site) during pre-puberty (p = 2.86 × 10(-8)) and rs872256 during puberty (p = 8.67 × 10(-9)). Several SNP '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 SNPs in any of the three epochs and adult BP related SNPs.

CONCLUSIONS: -Our results suggest that genetic determinants of blood pressure act from childhood, develop over the lifecourse, and show some evidence of age-specific effects.

Original language	English
Journal	Circulation: Cardiovascular Genetics
DOIs	https://doi.org/10.1161/CIRCGENETICS.115.001190
Publication status	Published - 11 Mar 2016

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10.1161/CIRCGENETICS.115.001190

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Laura Howe Population Health Scientist Fellowship
Howe, L. D. (Principal Investigator)
1/09/15 → 31/12/22
Project: Research
IEU Theme 3
Windmeijer, F. (Principal Investigator), Tilling, K. M. (Researcher) & Tilling, K. M. (Principal Investigator)
1/06/13 → 31/03/18
Project: Research
MRC UoB UNITE Unit - programme 3
Timpson, N. J. (Principal Investigator) & Timpson, N. J. (Principal Investigator)
1/06/13 → 31/03/18
Project: Research

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Parmar, P. G., Taal, H. R., Timpson, N. J., Thiering, E., Lehtimäki, T., Marinelli, M., Lind, P. A., Howe, L. D., Verwoert, G., Aalto, V., Uitterlinden, A. G., Briollais, L., Evans, D. M., Wright, M. J., Newnham, J. P., Whitfield, J. B., Lyytikäinen, L.-P., Rivadeneira, F., Boomsma, D. I., ... EArly Genetics and Lifecourse Epidemiology Consortium (2016). International GWAS Consortium Identifies Novel Loci Associated with Blood Pressure in Children and Adolescents. Circulation: Cardiovascular Genetics. https://doi.org/10.1161/CIRCGENETICS.115.001190

@article{9dc8a98bf1e044c88ed7d7fdb8919a58,

title = "International GWAS 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 EAGLE ( EA: rly G: enetics and L: ifecourse E: pidemiology) Consortium was meta-analysed across three 'epochs'; pre-puberty [4-7 years], puberty [8-12 years] and post-puberty [13-20 years]. Two novel loci were identified as having genome-wide associations with systolic blood pressure across specific age epochs; rs1563894 (ITGA11, located in active H3K27Ac mark and transcription factor CHiP and CpG methylation site) during pre-puberty (p = 2.86 {\texttimes} 10(-8)) and rs872256 during puberty (p = 8.67 {\texttimes} 10(-9)). Several SNP 'clusters' were also associated with childhood BP at p < 5 {\texttimes} 10(-3). Using a p-value threshold of < 5 {\texttimes} 10(-3) we found some overlap in variants across the different age epochs within our study, and between several SNPs in any of the three epochs and adult BP related SNPs.CONCLUSIONS: -Our results suggest that genetic determinants of blood pressure act from childhood, develop over the lifecourse, and show some evidence of age-specific effects.",

author = "Parmar, \{Priyakumari Ganesh\} and Taal, \{H Rob\} and Timpson, \{Nicholas J\} and Elisabeth Thiering and Terho Lehtim{\"a}ki and Marcella Marinelli and Lind, \{Penelope A\} and Howe, \{Laura D\} and Germaine Verwoert and Ville Aalto and Uitterlinden, \{Andr{\'e} G\} and Laurent Briollais and Evans, \{David M\} and Wright, \{Margaret J\} and Newnham, \{John P\} and Whitfield, \{John B\} and Leo-Pekka Lyytik{\"a}inen and Fernando Rivadeneira and Boomsma, \{Dorret I\} and Jorma Viikari and Gillman, \{Matthew W\} and \{St Pourcain\}, Beate and Jouke-Jan Hottenga and Montgomery, \{Grant W\} and Albert Hofman and Mika K{\"a}h{\"o}nen and Martin, \{Nicholas G\} and Tobin, \{Martin D\} and Olli Raitakari and Jesus Vioque and Jaddoe, \{Vincent W V\} and Marjo-Riitta Jarvelin and Beilin, \{Lawrence J\} and Joachim Heinrich and \{van Duijn\}, \{Cornelia M\} and Pennell, \{Craig E\} and Lawlor, \{Debbie A\} and Palmer, \{Lyle J\} and \{EArly Genetics and Lifecourse Epidemiology Consortium\}",

year = "2016",

month = mar,

day = "11",

doi = "10.1161/CIRCGENETICS.115.001190",

language = "English",

journal = "Circulation: Cardiovascular Genetics",

issn = "1942-325X",

publisher = "Lippincott Williams and Wilkins",

}

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 2016, 'International GWAS Consortium Identifies Novel Loci Associated with Blood Pressure in Children and Adolescents', Circulation: Cardiovascular Genetics. https://doi.org/10.1161/CIRCGENETICS.115.001190

TY - JOUR

T1 - International GWAS Consortium Identifies Novel Loci Associated with Blood Pressure in Children and Adolescents

AU - Parmar, Priyakumari Ganesh

AU - Taal, H Rob

AU - Timpson, Nicholas J

AU - Thiering, Elisabeth

AU - Lehtimäki, Terho

AU - Marinelli, Marcella

AU - Lind, Penelope A

AU - Howe, Laura D

AU - Verwoert, Germaine

AU - Aalto, Ville

AU - Uitterlinden, André G

AU - Briollais, Laurent

AU - Evans, David M

AU - Wright, Margaret J

AU - Newnham, John P

AU - Whitfield, John B

AU - Lyytikäinen, Leo-Pekka

AU - Rivadeneira, Fernando

AU - Boomsma, Dorret I

AU - Viikari, Jorma

AU - Gillman, Matthew W

AU - St Pourcain, Beate

AU - Hottenga, Jouke-Jan

AU - Montgomery, Grant W

AU - Hofman, Albert

AU - Kähönen, Mika

AU - Martin, Nicholas G

AU - Tobin, Martin D

AU - Raitakari, Olli

AU - Vioque, Jesus

AU - Jaddoe, Vincent W V

AU - Jarvelin, Marjo-Riitta

AU - Beilin, Lawrence J

AU - Heinrich, Joachim

AU - van Duijn, Cornelia M

AU - Pennell, Craig E

AU - Lawlor, Debbie A

AU - Palmer, Lyle J

AU - EArly Genetics and Lifecourse Epidemiology Consortium

PY - 2016/3/11

Y1 - 2016/3/11

N2 - 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 EAGLE ( EA: rly G: enetics and L: ifecourse E: pidemiology) Consortium was meta-analysed across three 'epochs'; pre-puberty [4-7 years], puberty [8-12 years] and post-puberty [13-20 years]. Two novel loci were identified as having genome-wide associations with systolic blood pressure across specific age epochs; rs1563894 (ITGA11, located in active H3K27Ac mark and transcription factor CHiP and CpG methylation site) during pre-puberty (p = 2.86 × 10(-8)) and rs872256 during puberty (p = 8.67 × 10(-9)). Several SNP '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 SNPs in any of the three epochs and adult BP related SNPs.CONCLUSIONS: -Our results suggest that genetic determinants of blood pressure act from childhood, develop over the lifecourse, and show some evidence of age-specific effects.

AB - 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 EAGLE ( EA: rly G: enetics and L: ifecourse E: pidemiology) Consortium was meta-analysed across three 'epochs'; pre-puberty [4-7 years], puberty [8-12 years] and post-puberty [13-20 years]. Two novel loci were identified as having genome-wide associations with systolic blood pressure across specific age epochs; rs1563894 (ITGA11, located in active H3K27Ac mark and transcription factor CHiP and CpG methylation site) during pre-puberty (p = 2.86 × 10(-8)) and rs872256 during puberty (p = 8.67 × 10(-9)). Several SNP '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 SNPs in any of the three epochs and adult BP related SNPs.CONCLUSIONS: -Our results suggest that genetic determinants of blood pressure act from childhood, develop over the lifecourse, and show some evidence of age-specific effects.

U2 - 10.1161/CIRCGENETICS.115.001190

DO - 10.1161/CIRCGENETICS.115.001190

M3 - Article (Academic Journal)

C2 - 26969751

SN - 1942-325X

JO - Circulation: Cardiovascular Genetics

JF - Circulation: Cardiovascular Genetics

ER -

International GWAS Consortium Identifies Novel Loci Associated with Blood Pressure in Children and Adolescents

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Projects

Laura Howe Population Health Scientist Fellowship

IEU Theme 3

MRC UoB UNITE Unit - programme 3

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