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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.

SUBMITTER: Wain LV 

PROVIDER: S-EPMC5783787 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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

Wain Louise V LV   Vaez Ahmad A   Jansen Rick R   Joehanes Roby R   van der Most Peter J PJ   Erzurumluoglu A Mesut AM   O'Reilly Paul F PF   Cabrera Claudia P CP   Warren Helen R HR   Rose Lynda M LM   Verwoert Germaine C GC   Hottenga Jouke-Jan JJ   Strawbridge Rona J RJ   Esko Tonu T   Arking Dan E DE   Hwang Shih-Jen SJ   Guo Xiuqing X   Kutalik Zoltan Z   Trompet Stella S   Shrine Nick N   Teumer Alexander A   Ried Janina S JS   Bis Joshua C JC   Smith Albert V AV   Amin Najaf N   Nolte Ilja M IM   Lyytikäinen Leo-Pekka LP   Mahajan Anubha A   Wareham Nicholas J NJ   Hofer Edith E   Joshi Peter K PK   Kristiansson Kati K   Traglia Michela M   Havulinna Aki S AS   Goel Anuj A   Nalls Mike A MA   Sõber Siim S   Vuckovic Dragana D   Luan Jian'an J   Del Greco M Fabiola F   Ayers Kristin L KL   Marrugat Jaume J   Ruggiero Daniela D   Lopez Lorna M LM   Niiranen Teemu T   Enroth Stefan S   Jackson Anne U AU   Nelson Christopher P CP   Huffman Jennifer E JE   Zhang Weihua W   Marten Jonathan J   Gandin Ilaria I   Harris Sarah E SE   Zemunik Tatijana T   Lu Yingchang Y   Evangelou Evangelos E   Shah Nabi N   de Borst Martin H MH   Mangino Massimo M   Prins Bram P BP   Campbell Archie A   Li-Gao Ruifang R   Chauhan Ganesh G   Oldmeadow Christopher C   Abecasis Gonçalo G   Abedi Maryam M   Barbieri Caterina M CM   Barnes Michael R MR   Batini Chiara C   Beilby John J   Blake Tineka T   Boehnke Michael M   Bottinger Erwin P EP   Braund Peter S PS   Brown Morris M   Brumat Marco M   Campbell Harry H   Chambers John C JC   Cocca Massimiliano M   Collins Francis F   Connell John J   Cordell Heather J HJ   Damman Jeffrey J JJ   Davies Gail G   de Geus Eco J EJ   de Mutsert Renée R   Deelen Joris J   Demirkale Yusuf Y   Doney Alex S F ASF   Dörr Marcus M   Farrall Martin M   Ferreira Teresa T   Frånberg Mattias M   Gao He H   Giedraitis Vilmantas V   Gieger Christian C   Giulianini Franco F   Gow Alan J AJ   Hamsten Anders A   Harris Tamara B TB   Hofman Albert A   Holliday Elizabeth G EG   Hui Jennie J   Jarvelin Marjo-Riitta MR   Johansson Åsa Å   Johnson Andrew D AD   Jousilahti Pekka P   Jula Antti A   Kähönen Mika M   Kathiresan Sekar S   Khaw Kay-Tee KT   Kolcic Ivana I   Koskinen Seppo S   Langenberg Claudia C   Larson Marty M   Launer Lenore J LJ   Lehne Benjamin B   Liewald David C M DCM   Lin Li L   Lind Lars L   Mach François F   Mamasoula Chrysovalanto C   Menni Cristina C   Menni Cristina C   Mifsud Borbala B   Milaneschi Yuri Y   Morgan Anna A   Morris Andrew D AD   Morrison Alanna C AC   Munson Peter J PJ   Nandakumar Priyanka P   Nguyen Quang Tri QT   Nutile Teresa T   Oldehinkel Albertine J AJ   Oostra Ben A BA   Org Elin E   Org Elin E   Padmanabhan Sandosh S   Palotie Aarno A   Paré Guillaume G   Pattie Alison A   Penninx Brenda W J H BWJH   Poulter Neil N   Pramstaller Peter P PP   Raitakari Olli T OT   Ren Meixia M   Rice Kenneth K   Ridker Paul M PM   Riese Harriëtte H   Ripatti Samuli S   Robino Antonietta A   Rotter Jerome I JI   Rudan Igor I   Saba Yasaman Y   Saint Pierre Aude A   Sala Cinzia F CF   Sarin Antti-Pekka AP   Schmidt Reinhold R   Scott Rodney R   Seelen Marc A MA   Shields Denis C DC   Siscovick David D   Sorice Rossella R   Stanton Alice A   Stott David J DJ   Sundström Johan J   Swertz Morris M   Taylor Kent D KD   Thom Simon S   Tzoulaki Ioanna I   Tzourio Christophe C   Uitterlinden André G AG   Uitterlinden André G AG   Völker Uwe U   Vollenweider Peter P   Wild Sarah S   Willemsen Gonneke G   Wright Alan F AF   Yao Jie J   Thériault Sébastien S   Conen David D   Attia John J   Sever Peter P   Debette Stéphanie S   Mook-Kanamori Dennis O DO   Zeggini Eleftheria E   Spector Tim D TD   van der Harst Pim P   Palmer Colin N A CNA   Vergnaud Anne-Claire AC   Loos Ruth J F RJF   Polasek Ozren O   Polasek Ozren O   Starr John M JM   Girotto Giorgia G   Hayward Caroline C   Kooner Jaspal S JS   Lindgren Cecila M CM   Vitart Veronique V   Samani Nilesh J NJ   Tuomilehto Jaakko J   Gyllensten Ulf U   Knekt Paul P   Deary Ian J IJ   Ciullo Marina M   Elosua Roberto R   Elosua Roberto R   Keavney Bernard D BD   Hicks Andrew A AA   Scott Robert A RA   Gasparini Paolo P   Laan Maris M   Liu YongMei Y   Watkins Hugh H   Hartman Catharina A CA   Salomaa Veikko V   Toniolo Daniela D   Perola Markus M   Wilson James F JF   Schmidt Helena H   Zhao Jing Hua JH   Lehtimäki Terho T   Lehtimäki Terho T   van Duijn Cornelia M CM   Gudnason Vilmundur V   Psaty Bruce M BM   Peters Annette A   Rettig Rainer R   James Alan A   Jukema J Wouter JW   Strachan David P DP   Palmas Walter W   Metspalu Andres A   Ingelsson Erik E   Boomsma Dorret I DI   Franco Oscar H OH   Bochud Murielle M   Newton-Cheh Christopher C   Munroe Patricia B PB   Elliott Paul P   Chasman Daniel I DI   Chakravarti Aravinda A   Knight Joanne J   Morris Andrew P AP   Levy Daniel D   Tobin Martin D MD   Snieder Harold H   Caulfield Mark J MJ   Ehret Georg B GB  

Hypertension (Dallas, Tex. : 1979) 20170724 3


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 n  ...[more]

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