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

Gasparini Paolo

Research output: Contribution to journalArticle

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 nearHSPB7,TNXB,LRP12,LOC283335,SEPT9, andAKT2, and provide new replication evidence for a further 2 signals inEBF2andNFKBIACombining 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 languageEnglish
JournalHypertension
DOIs
Publication statusE-pub ahead of print - Jul 24 2017

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Genome-Wide Association Study
Genetic Association Studies
Blood Pressure
Kidney
Genes
Cardiovascular Diseases
Genome
Pharmacology
Hypertension
Gene Expression
Datasets
Therapeutics

Cite this

@article{46fbab68fd2d47c28e2bf3e3873fda4e,
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 nearHSPB7,TNXB,LRP12,LOC283335,SEPT9, andAKT2, and provide new replication evidence for a further 2 signals inEBF2andNFKBIACombining 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.",
author = "{Gasparini Paolo} 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 Lyytik{\"a}inen and Anubha Mahajan and Wareham, {Nicholas J} and Edith Hofer and Joshi, {Peter K} and Kati Kristiansson and Michela Traglia and Havulinna, {Aki S} and Anuj Goel and Nalls, {Mike A} and Siim S{\~o}ber and Dragana Vuckovic and Jian'an Luan and {Del Greco M}, Fabiola and Ayers, {Kristin L} and Jaume Marrugat and Daniela Ruggiero and Lopez, {Lorna M} and Barbieri, {Caterina M} and Antonietta Robino and Sala, {Cinzia F} and Marina Ciullo and Paolo Gasparini and Daniela Toniolo",
note = "{\circledC} 2017 American Heart Association, Inc.",
year = "2017",
month = "7",
day = "24",
doi = "10.1161/HYPERTENSIONAHA.117.09438",
language = "English",
journal = "Hypertension",
issn = "0194-911X",
publisher = "Lippincott Williams and Wilkins",

}

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 - Gasparini Paolo

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 - Lyytikäinen, Leo-Pekka

AU - Mahajan, Anubha

AU - Wareham, Nicholas J

AU - Hofer, Edith

AU - Joshi, Peter K

AU - Kristiansson, Kati

AU - Traglia, Michela

AU - Havulinna, Aki S

AU - Goel, Anuj

AU - Nalls, Mike A

AU - Sõber, Siim

AU - Vuckovic, Dragana

AU - Luan, Jian'an

AU - Del Greco M, Fabiola

AU - Ayers, Kristin L

AU - Marrugat, Jaume

AU - Ruggiero, Daniela

AU - Lopez, Lorna M

AU - Barbieri, Caterina M

AU - Robino, Antonietta

AU - Sala, Cinzia F

AU - Ciullo, Marina

AU - Gasparini, Paolo

AU - Toniolo, Daniela

N1 - © 2017 American Heart Association, Inc.

PY - 2017/7/24

Y1 - 2017/7/24

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 nearHSPB7,TNXB,LRP12,LOC283335,SEPT9, andAKT2, and provide new replication evidence for a further 2 signals inEBF2andNFKBIACombining 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 nearHSPB7,TNXB,LRP12,LOC283335,SEPT9, andAKT2, and provide new replication evidence for a further 2 signals inEBF2andNFKBIACombining 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.

U2 - 10.1161/HYPERTENSIONAHA.117.09438

DO - 10.1161/HYPERTENSIONAHA.117.09438

M3 - Article

C2 - 28739976

JO - Hypertension

JF - Hypertension

SN - 0194-911X

ER -