Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney

BIOS Consortium; Lifelines Cohort Study; Understanding Soc Sci Grp; Louise V. Wain; Ahmad Vaez; Rick Jansen; Roby Joehanes; Peter J. van der Most; A. Mesut Erzurumluoglu; Paul F. O'Reilly; Claudia P. Cabrera; Helen R. Warren; Lynda M. Rose; Germaine C. Verwoert; Jouke-Jan Hottenga; Rona J. Strawbridge; Tonu Esko; Dan E. Arking; Shih-Jen Hwang; Xiuqing Guo; Zoltan Kutalik; Stella Trompet; Nick Shrine; Alexander Teumer; Janina S. Ried; Joshua C. Bis; Albert V. Smith; Najaf Amin; Ilja M. Nolte; Leo-Pekka Lyytikainen; Anubha Mahajan; Nicholas J. Wareham; Edith Hofer; Peter K. Joshi; Kati Kristiansson; Michela Traglia; Jonathan Marten; Sarah E. Harris; Archie Campbell; Harry Campbell; Gail Davies; David C. M. Liewald; Andrew D. Morris; Alison Pattie; Igor Rudan; Sarah Wild; Alan F. Wright; John M. Starr; Caroline Hayward; Veronique Vitart; Ian J. Deary; James F. Wilson; Andrew P. Morris

doi:10.1161/HYPERTENSIONAHA.117.09438

Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney

BIOS Consortium, Lifelines Cohort Study, Understanding Soc Sci Grp, Louise V. Wain, Ahmad Vaez, Rick Jansen, Roby Joehanes, Peter J. van der Most, A. Mesut Erzurumluoglu, Paul F. O'Reilly, Claudia P. Cabrera, Helen R. Warren, Lynda M. Rose, Germaine C. Verwoert, Jouke-Jan Hottenga, Rona J. Strawbridge, Tonu Esko, Dan E. Arking, Shih-Jen Hwang, Xiuqing GuoZoltan Kutalik, Stella Trompet, Nick Shrine, Alexander Teumer, Janina S. Ried, Joshua C. Bis, Albert V. Smith, Najaf Amin, Ilja M. Nolte, Leo-Pekka Lyytikainen, Anubha Mahajan, Nicholas J. Wareham, Edith Hofer, Peter K. Joshi, Kati Kristiansson, Michela Traglia, Jonathan Marten, Sarah E. Harris, Archie Campbell, Harry Campbell, Gail Davies, David C. M. Liewald, Andrew D. Morris, Alison Pattie, Igor Rudan, Sarah Wild, Alan F. Wright, John M. Starr, Caroline Hayward, Veronique Vitart, Ian J. Deary, James F. Wilson, Andrew P. Morris

Research output: Contribution to journal › Article › peer-review

Abstract

Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA. Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation.

Original language	English
Pages (from-to)	E4-E19
Number of pages	49
Journal	Hypertension
Volume	70
Issue number	3
Early online date	24 Jul 2017
DOIs	https://doi.org/10.1161/HYPERTENSIONAHA.117.09438
Publication status	Published - Sept 2017

Keywords / Materials (for Non-textual outputs)

blood pressure
cardiovascular risk
complex traits
eSNP
GWAS
hypertension
PERIPHERAL-BLOOD
COMMON VARIANTS
PULSE PRESSURE
CENTRIC ARRAY
HYPERTENSION
INDIVIDUALS
TRAITS
METAANALYSIS
NETHERLANDS
TARGET

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10.1161/HYPERTENSIONAHA.117.09438

Novel blood pressure locus and gene discovery using GWAS and expression datasets from blood and the kidneyAccepted author manuscript, 580 KB

http://hyper.ahajournals.org/lookup/doi/10.1161/HYPERTENSIONAHA.117.09438

The Disconnected Mind Phase 3
Cox, S. (Principal Investigator) & Deary, I. (Co-investigator)
1/04/16 → 31/03/23
Project: Research
Brain imaging and cognitive ageing in the Lothian Birth Cohort 1936: III
Wardlaw, J. (Principal Investigator), Bastin, M. (Co-investigator) & Deary, I. (Co-investigator)
MRC
1/05/15 → 30/04/19
Project: Research
RA2661 Centre for Cognitive Ageing and Cognitive Epidemiology Phase 2. Main Budget.
Deary, I. (Principal Investigator), Gale, C. (Co-investigator), Holmes, M. (Co-investigator), Logie, P. (Co-investigator), Maclullich, A. (Co-investigator), Porteous, D. (Co-investigator), Seckl, J. (Co-investigator), Starr, J. (Co-investigator), Wardlaw, J. (Co-investigator) & Okely, J. (Researcher)
1/09/13 → 31/08/19
Project: Research

Cite this

BIOS Consortium, Lifelines Cohort Study, Understanding Soc Sci Grp, Wain, L. V., Vaez, A., Jansen, R., Joehanes, R., van der Most, P. J., Erzurumluoglu, A. M., O'Reilly, P. F., Cabrera, C. P., Warren, H. R., Rose, L. M., Verwoert, G. C., Hottenga, J.-J., Strawbridge, R. J., Esko, T., Arking, D. E., Hwang, S.-J., ... Morris, A. P. (2017). Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney. Hypertension, 70(3), E4-E19. https://doi.org/10.1161/HYPERTENSIONAHA.117.09438

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title = "Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney",

abstract = "Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA. Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation.",

keywords = "blood pressure, cardiovascular risk, complex traits, eSNP, GWAS, hypertension, PERIPHERAL-BLOOD, COMMON VARIANTS, PULSE PRESSURE, CENTRIC ARRAY, HYPERTENSION, INDIVIDUALS, TRAITS, METAANALYSIS, NETHERLANDS, TARGET",

author = "\{BIOS Consortium\} and \{Lifelines Cohort Study\} and \{Understanding Soc Sci Grp\} and Wain, \{Louise V.\} and Ahmad Vaez and Rick Jansen and Roby Joehanes and \{van der Most\}, \{Peter J.\} and Erzurumluoglu, \{A. Mesut\} and O'Reilly, \{Paul F.\} and Cabrera, \{Claudia P.\} and Warren, \{Helen R.\} and Rose, \{Lynda M.\} and Verwoert, \{Germaine C.\} and Jouke-Jan Hottenga and Strawbridge, \{Rona J.\} and Tonu Esko and Arking, \{Dan E.\} and Shih-Jen Hwang and Xiuqing Guo and Zoltan Kutalik and Stella Trompet and Nick Shrine and Alexander Teumer and Ried, \{Janina S.\} and Bis, \{Joshua C.\} and Smith, \{Albert V.\} and Najaf Amin and Nolte, \{Ilja M.\} and Leo-Pekka Lyytikainen and Anubha Mahajan and Wareham, \{Nicholas J.\} and Edith Hofer and Joshi, \{Peter K.\} and Kati Kristiansson and Michela Traglia and Jonathan Marten and Harris, \{Sarah E.\} and Archie Campbell and Harry Campbell and Gail Davies and Liewald, \{David C. M.\} and Morris, \{Andrew D.\} and Alison Pattie and Igor Rudan and Sarah Wild and Wright, \{Alan F.\} and Starr, \{John M.\} and Caroline Hayward and Veronique Vitart and Deary, \{Ian J.\} and Wilson, \{James F.\} and Morris, \{Andrew P.\}",

year = "2017",

month = sep,

doi = "10.1161/HYPERTENSIONAHA.117.09438",

language = "English",

volume = "70",

pages = "E4--E19",

journal = "Hypertension",

issn = "0194-911X",

publisher = "Lippincott Williams and Wilkins",

number = "3",

}

BIOS Consortium, Lifelines Cohort Study, Understanding Soc Sci Grp, Wain, LV, Vaez, A, Jansen, R, Joehanes, R, van der Most, PJ, Erzurumluoglu, AM, O'Reilly, PF, Cabrera, CP, Warren, HR, Rose, LM, Verwoert, GC, Hottenga, J-J, Strawbridge, RJ, Esko, T, Arking, DE, Hwang, S-J, Guo, X, Kutalik, Z, Trompet, S, Shrine, N, Teumer, A, Ried, JS, Bis, JC, Smith, AV, Amin, N, Nolte, IM, Lyytikainen, L-P, Mahajan, A, Wareham, NJ, Hofer, E, Joshi, PK, Kristiansson, K, Traglia, M, Marten, J, Harris, SE , Campbell, A , Campbell, H , Davies, G, Liewald, DCM, Morris, AD, Pattie, A, Rudan, I , Wild, S, Wright, AF, Starr, JM, Hayward, C, Vitart, V, Deary, IJ , Wilson, JF & Morris, AP 2017, 'Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney', Hypertension, vol. 70, no. 3, pp. E4-E19. https://doi.org/10.1161/HYPERTENSIONAHA.117.09438

TY - JOUR

T1 - Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney

AU - BIOS Consortium

AU - Lifelines Cohort Study

AU - Understanding Soc Sci Grp

AU - Wain, Louise V.

AU - Vaez, Ahmad

AU - Jansen, Rick

AU - Joehanes, Roby

AU - van der Most, Peter J.

AU - Erzurumluoglu, A. Mesut

AU - O'Reilly, Paul F.

AU - Cabrera, Claudia P.

AU - Warren, Helen R.

AU - Rose, Lynda M.

AU - Verwoert, Germaine C.

AU - Hottenga, Jouke-Jan

AU - Strawbridge, Rona J.

AU - Esko, Tonu

AU - Arking, Dan E.

AU - Hwang, Shih-Jen

AU - Guo, Xiuqing

AU - Kutalik, Zoltan

AU - Trompet, Stella

AU - Shrine, Nick

AU - Teumer, Alexander

AU - Ried, Janina S.

AU - Bis, Joshua C.

AU - Smith, Albert V.

AU - Amin, Najaf

AU - Nolte, Ilja M.

AU - Lyytikainen, Leo-Pekka

AU - Mahajan, Anubha

AU - Wareham, Nicholas J.

AU - Hofer, Edith

AU - Joshi, Peter K.

AU - Kristiansson, Kati

AU - Traglia, Michela

AU - Marten, Jonathan

AU - Harris, Sarah E.

AU - Campbell, Archie

AU - Campbell, Harry

AU - Davies, Gail

AU - Liewald, David C. M.

AU - Morris, Andrew D.

AU - Pattie, Alison

AU - Rudan, Igor

AU - Wild, Sarah

AU - Wright, Alan F.

AU - Starr, John M.

AU - Hayward, Caroline

AU - Vitart, Veronique

AU - Deary, Ian J.

AU - Wilson, James F.

AU - Morris, Andrew P.

PY - 2017/9

Y1 - 2017/9

N2 - Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA. Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation.

AB - Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA. Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation.

KW - blood pressure

KW - cardiovascular risk

KW - complex traits

KW - eSNP

KW - GWAS

KW - hypertension

KW - PERIPHERAL-BLOOD

KW - COMMON VARIANTS

KW - PULSE PRESSURE

KW - CENTRIC ARRAY

KW - HYPERTENSION

KW - INDIVIDUALS

KW - TRAITS

KW - METAANALYSIS

KW - NETHERLANDS

KW - TARGET

U2 - 10.1161/HYPERTENSIONAHA.117.09438

DO - 10.1161/HYPERTENSIONAHA.117.09438

M3 - Article

SN - 0194-911X

VL - 70

SP - E4-E19

JO - Hypertension

JF - Hypertension

IS - 3

ER -

Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney

Abstract

Keywords / Materials (for Non-textual outputs)

Access to Document

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Projects

The Disconnected Mind Phase 3

Brain imaging and cognitive ageing in the Lothian Birth Cohort 1936: III

RA2661 Centre for Cognitive Ageing and Cognitive Epidemiology Phase 2. Main Budget.

Cite this