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 BP 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 (US) |
|---|---|
| Journal | Unknown Journal |
| DOIs | |
| State | Published - Feb 22 2017 |
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Agricultural and Biological Sciences(all)
- Immunology and Microbiology(all)
- Neuroscience(all)
- Pharmacology, Toxicology and Pharmaceutics(all)
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Novel blood pressure locus and gene discovery using GWAS and expression datasets from blood and the kidney. / Wain, Louise V.; Vaez, Ahmad; Jansen, Rick; Joehanes, Roby; van der Most, Peter J.; Erzurumluoglu, A. Mesut; O'Reilly, Paul; Cabrera, Claudia P.; Warren, Helen R.; Rose, Lynda M.; Verwoert, Germaine C.; Hottenga, Jouke Jan; Strawbridge, Rona J.; Esko, Tonu; Arking, Dan E.; Hwang, Shih Jen; Guo, Xiuqing; Kutalik, Zoltan; Trompet, Stella; Shrine, Nick; Teumer, Alexander; Ried, Janina S.; Bis, Joshua C.; Smith, Albert V.; Amin, Najaf; Nolte, Ilja M.; Lyytikäinen, Leo Pekka; Mahajan, Anubha; Wareham, Nicholas J.; Hofer, Edith; Joshi, Peter K.; Kristiansson, Kati; Traglia, Michela; Havulinna, Aki S.; Goel, Anuj; Nalls, Mike A.; Sõber, Siim; Vuckovic, Dragana; Luan, Jian'an; Del Greco, Fabiola; Ayers, Kristin L.; Marrugat, Jaume; Ruggiero, Daniela; Lopez, Lorna M.; Niiranen, Teemu; Enroth, Stefan; Jackson, Anne U.; Nelson, Christopher P.; Huffman, Jennifer E.; Zhang, Weihua; Marten, Jonathan; Gandin, Ilaria; Harris, Sarah E.; Zemonik, Tatijana; Lu, Yingchang; Evangelou, Evangelos; Shah, Nabi; de Borst, Martin H.; Mangino, Massimo; Prins, Bram P.; Campbell, Archie; Li-Gao, Ruifang; Chauhan, Ganesh; Oldmeadow, Christopher; Abecasis, Gonçalo; Abedi, Maryam; Barbieri, Caterina M.; Barnes, Michael R.; Batini, Chiara; Beilby, John; Blake, Tineka; Boehnke, Michael; Bottinger, Erwin P.; Braund, Peter S.; Brown, Morris; Brumat, Marco; Campbell, Harry; Chambers, John C.; Cocca, Massimiliano; Collins, Francis; Connell, John; Cordell, Heather J.; Damman, Jeffrey J.; Davies, Gail; de Geus, Eco J.; de Mutsert, Renée; Deelen, Joris; Demirkale, Yusuf; Doney, Alex S.F.; Dörr, Marcus; Farrall, Martin; Ferreira, Teresa; Frånberg, Mattias; Gao, He; Giedraitis, Vilmantas; Gieger, Christian; Giulianini, Franco; Gow, Alan J.; Hamsten, Anders; Harris, Tamara B.; Hofman, Albert; Holliday, Elizabeth G.; Hui, Jennie; Jarvelin, Marjo Riitta; Johansson, Åsa; Johnson, Andrew D.; Jousilahti, Pekka; Jula, Antti; Kähönen, Mika; Kathiresan, Sekar; Khaw, Kay Tee; Kolcic, Ivana; Koskinen, Seppo; Langenberg, Claudia; Larson, Marty; Launer, Lenore J.; Lehne, Benjamin; Liewald, David C.M.; Lin, Li; Lind, Lars; Mach, François; Mamasoula, Chrysovalanto; Menni, Cristina; Mifsud, Borbala; Milaneschi, Yuri; Morgan, Anna; Morris, Andrew D.; Morrison, Alanna C.; Munson, Peter J.; Nandakumar, Priyanka; Nguyen, Quang Tri; Nutile, Teresa; Oldehinkel, Albertine J.; Oostra, Ben A.; Org, Elin; Padmanabhan, Sandosh; Palotie, Aarno; Paré, Guillaume; Pattie, Alison; Penninx, Brenda W.J.H.; Poulter, Neil; Pramstaller, Peter P.; Raitakari, Olli T.; Ren, Meixia; Rice, Kenneth; Ridker, Paul M.; Riese, Harriëtte; Ripatti, Samuli; Robino, Antonietta; Rotter, Jerome I.; Rudan, Igor; Saba, Yasaman; Pierre, Aude Saint; Sala, Cinzia F.; Sarin, Antti Pekka; Schmidt, Reinhold; Scott, Rodney; Seelen, Marc A.; Shields, Denis C.; Siscovick, David; Sorice, Rossella; Stanton, Alice; Stott, David J.; Sundström, Johan; Swertz, Morris; Taylor, Kent D.; Thom, Simon; Tzoulaki, Ioanna; Tzourio, Christophe; Uitterlinden, André G.; Vöker, Uwe; Vollenweider, Peter; Wild, Sarah; Willemsen, Gonneke; Wright, Alan F.; Yao, Jie; Thériault, Sébastien; Conen, David; John, Attia; Sever, Peter; Debette, Stéphanie; Mook-Kanamori, Dennis O.; Zeggini, Eleftheria; Spector, Tim D.; van der Harst, Pim; Palmer, Colin N.A.; Vergnaud, Anne Claire; Loos, Ruth J.F.; Polasek, Ozren; Starr, John M.; Girotto, Giorgia; Hayward, Caroline; Kooner, Jaspal S.; Lindgren, Cecila M.; Vitart, Veronique; Samani, Nilesh J.; Tuomilehto, Jaakko; Gyllensten, Ulf; Knekt, Paul; Deary, Ian J.; Ciullo, Marina; Elosua, Roberto; Keavney, Bernard D.; Hicks, Andrew A.; Scott, Robert A.; Gasparini, Paolo; Laan, Maris; Liu, Yong Mei; Watkins, Hugh; Hartman, Catharina A.; Salomaa, Veikko; Toniolo, Daniela; Perola, Markus; Wilson, James F.; Schmidt, Helena; Zhao, Jing Hua; Lehtimäki, Terho; van Duijn, Cornelia M.; Gudnason, Vilmundur; Psaty, Bruce M.; Peters, Annette; Rettig, Rainer; James, Alan; Jukema, J. Wouter; Strachan, David P.; Palmas, Walter; Metspalu, Andres; Ingelsson, Erik; Boomsma, Dorret I.; Franco, Oscar H.; Bochud, Murielle; Newton-Cheh, Christopher; Munroe, Patricia B.; Elliott, Paul; Chasman, Daniel I.; Chakravarti, Aravinda; Knight, Joanne; Morris, Andrew P.; Levy, Daniel; Tobin, Martin D.; Snieder, Harold; Caulfield, Mark J.; Ehret, Georg.
In: Unknown Journal, 22.02.2017.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Novel blood pressure locus and gene discovery using GWAS and expression datasets from blood and the kidney
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
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, Fabiola
AU - Ayers, Kristin L.
AU - Marrugat, Jaume
AU - Ruggiero, Daniela
AU - Lopez, Lorna M.
AU - Niiranen, Teemu
AU - Enroth, Stefan
AU - Jackson, Anne U.
AU - Nelson, Christopher P.
AU - Huffman, Jennifer E.
AU - Zhang, Weihua
AU - Marten, Jonathan
AU - Gandin, Ilaria
AU - Harris, Sarah E.
AU - Zemonik, Tatijana
AU - Lu, Yingchang
AU - Evangelou, Evangelos
AU - Shah, Nabi
AU - de Borst, Martin H.
AU - Mangino, Massimo
AU - Prins, Bram P.
AU - Campbell, Archie
AU - Li-Gao, Ruifang
AU - Chauhan, Ganesh
AU - Oldmeadow, Christopher
AU - Abecasis, Gonçalo
AU - Abedi, Maryam
AU - Barbieri, Caterina M.
AU - Barnes, Michael R.
AU - Batini, Chiara
AU - Beilby, John
AU - Blake, Tineka
AU - Boehnke, Michael
AU - Bottinger, Erwin P.
AU - Braund, Peter S.
AU - Brown, Morris
AU - Brumat, Marco
AU - Campbell, Harry
AU - Chambers, John C.
AU - Cocca, Massimiliano
AU - Collins, Francis
AU - Connell, John
AU - Cordell, Heather J.
AU - Damman, Jeffrey J.
AU - Davies, Gail
AU - de Geus, Eco J.
AU - de Mutsert, Renée
AU - Deelen, Joris
AU - Demirkale, Yusuf
AU - Doney, Alex S.F.
AU - Dörr, Marcus
AU - Farrall, Martin
AU - Ferreira, Teresa
AU - Frånberg, Mattias
AU - Gao, He
AU - Giedraitis, Vilmantas
AU - Gieger, Christian
AU - Giulianini, Franco
AU - Gow, Alan J.
AU - Hamsten, Anders
AU - Harris, Tamara B.
AU - Hofman, Albert
AU - Holliday, Elizabeth G.
AU - Hui, Jennie
AU - Jarvelin, Marjo Riitta
AU - Johansson, Åsa
AU - Johnson, Andrew D.
AU - Jousilahti, Pekka
AU - Jula, Antti
AU - Kähönen, Mika
AU - Kathiresan, Sekar
AU - Khaw, Kay Tee
AU - Kolcic, Ivana
AU - Koskinen, Seppo
AU - Langenberg, Claudia
AU - Larson, Marty
AU - Launer, Lenore J.
AU - Lehne, Benjamin
AU - Liewald, David C.M.
AU - Lin, Li
AU - Lind, Lars
AU - Mach, François
AU - Mamasoula, Chrysovalanto
AU - Menni, Cristina
AU - Mifsud, Borbala
AU - Milaneschi, Yuri
AU - Morgan, Anna
AU - Morris, Andrew D.
AU - Morrison, Alanna C.
AU - Munson, Peter J.
AU - Nandakumar, Priyanka
AU - Nguyen, Quang Tri
AU - Nutile, Teresa
AU - Oldehinkel, Albertine J.
AU - Oostra, Ben A.
AU - Org, Elin
AU - Padmanabhan, Sandosh
AU - Palotie, Aarno
AU - Paré, Guillaume
AU - Pattie, Alison
AU - Penninx, Brenda W.J.H.
AU - Poulter, Neil
AU - Pramstaller, Peter P.
AU - Raitakari, Olli T.
AU - Ren, Meixia
AU - Rice, Kenneth
AU - Ridker, Paul M.
AU - Riese, Harriëtte
AU - Ripatti, Samuli
AU - Robino, Antonietta
AU - Rotter, Jerome I.
AU - Rudan, Igor
AU - Saba, Yasaman
AU - Pierre, Aude Saint
AU - Sala, Cinzia F.
AU - Sarin, Antti Pekka
AU - Schmidt, Reinhold
AU - Scott, Rodney
AU - Seelen, Marc A.
AU - Shields, Denis C.
AU - Siscovick, David
AU - Sorice, Rossella
AU - Stanton, Alice
AU - Stott, David J.
AU - Sundström, Johan
AU - Swertz, Morris
AU - Taylor, Kent D.
AU - Thom, Simon
AU - Tzoulaki, Ioanna
AU - Tzourio, Christophe
AU - Uitterlinden, André G.
AU - Vöker, Uwe
AU - Vollenweider, Peter
AU - Wild, Sarah
AU - Willemsen, Gonneke
AU - Wright, Alan F.
AU - Yao, Jie
AU - Thériault, Sébastien
AU - Conen, David
AU - John, Attia
AU - Sever, Peter
AU - Debette, Stéphanie
AU - Mook-Kanamori, Dennis O.
AU - Zeggini, Eleftheria
AU - Spector, Tim D.
AU - van der Harst, Pim
AU - Palmer, Colin N.A.
AU - Vergnaud, Anne Claire
AU - Loos, Ruth J.F.
AU - Polasek, Ozren
AU - Starr, John M.
AU - Girotto, Giorgia
AU - Hayward, Caroline
AU - Kooner, Jaspal S.
AU - Lindgren, Cecila M.
AU - Vitart, Veronique
AU - Samani, Nilesh J.
AU - Tuomilehto, Jaakko
AU - Gyllensten, Ulf
AU - Knekt, Paul
AU - Deary, Ian J.
AU - Ciullo, Marina
AU - Elosua, Roberto
AU - Keavney, Bernard D.
AU - Hicks, Andrew A.
AU - Scott, Robert A.
AU - Gasparini, Paolo
AU - Laan, Maris
AU - Liu, Yong Mei
AU - Watkins, Hugh
AU - Hartman, Catharina A.
AU - Salomaa, Veikko
AU - Toniolo, Daniela
AU - Perola, Markus
AU - Wilson, James F.
AU - Schmidt, Helena
AU - Zhao, Jing Hua
AU - Lehtimäki, Terho
AU - van Duijn, Cornelia M.
AU - Gudnason, Vilmundur
AU - Psaty, Bruce M.
AU - Peters, Annette
AU - Rettig, Rainer
AU - James, Alan
AU - Jukema, J. Wouter
AU - Strachan, David P.
AU - Palmas, Walter
AU - Metspalu, Andres
AU - Ingelsson, Erik
AU - Boomsma, Dorret I.
AU - Franco, Oscar H.
AU - Bochud, Murielle
AU - Newton-Cheh, Christopher
AU - Munroe, Patricia B.
AU - Elliott, Paul
AU - Chasman, Daniel I.
AU - Chakravarti, Aravinda
AU - Knight, Joanne
AU - Morris, Andrew P.
AU - Levy, Daniel
AU - Tobin, Martin D.
AU - Snieder, Harold
AU - Caulfield, Mark J.
AU - Ehret, Georg
N1 - Publisher Copyright: The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2017/2/22
Y1 - 2017/2/22
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 BP 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 BP 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.
UR - http://www.scopus.com/inward/record.url?scp=85095646324&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85095646324&partnerID=8YFLogxK
U2 - 10.1101/110833
DO - 10.1101/110833
M3 - Article
AN - SCOPUS:85095646324
JO - Advances in Water Resources
JF - Advances in Water Resources
SN - 0309-1708
ER -