Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk

Elevated blood pressure is the leading heritable risk factor for cardiovascular disease worldwide. We report genetic association of blood pressure (systolic, diastolic, pulse pressure) among UK Biobank participants of European ancestry with independent replication in other cohorts, and robust validation of 107 independent loci. We also identify new independent variants at 11 previously reported blood pressure loci. In combination with results from a range of in silico functional analyses and wet bench experiments, our findings highlight new biological pathways for blood pressure regulation enriched for genes expressed in vascular tissues and identify potential therapeutic targets for hypertension. Results from genetic risk score models raise the possibility of a precision medicine approach through early lifestyle intervention to offset the impact of blood pressure–raising genetic variants on future cardiovascular disease risk.

He Gao | Andres Metspalu | Fotios Drenos | Borbala Mifsud | Alice Stanton | Simon Thom | Marie Loh | Evangelos Evangelou | Nilesh J Samani | Reedik Mägi | Danish Saleheen | Caroline Hayward | Bernard Keavney | Ioanna Ntalla | Stephan J L Bakker | Ibrahim Karaman | Tõnu Esko | Harold Snieder | Praveen Surendran | Aravinda Chakravarti | Daniel Levy | Louise V Wain | Martin D Tobin | Martin Farrall | Sandosh Padmanabhan | Lorna M. Lopez | John C Chambers | Jiang He | Norihiro Kato | Daniel I Chasman | Pim van der Harst | Aude Saint Pierre | Denis C Shields | Jonathan Marten | Paul F O'Reilly | M. Jarvelin | M. Nalls | C. Gieger | O. Franco | D. Levy | I. Deary | L. Wain | N. Shrine | I. Ntalla | J. Cook | R. Mägi | E. Zeggini | D. Strachan | M. Tobin | G. Abecasis | K. Kristiansson | T. Lehtimäki | V. Salomaa | M. Perola | C. Lindgren | Z. Kutalik | M. Boehnke | P. Ridker | D. Chasman | N. Samani | P. Braund | M. Mangino | Morris J. Brown | J. Connell | P. Munroe | M. Caulfield | M. Farrall | T. Ferreira | V. Gudnason | D. Conen | A. Chakravarti | P. Munson | E. Tai | Stefan Enroth | A. James | Yongmei Liu | B. Psaty | D. Siscovick | A. Stanton | S. Wild | B. Penninx | G. Willemsen | D. Arking | A. Kraja | A. Palotie | S. Ripatti | A. Metspalu | T. Esko | H. Snieder | E. Ingelsson | A. Jackson | J. Tuomilehto | A. Doney | S. Kathiresan | C. Newton-Cheh | K. Taylor | J. Rotter | I. Karaman | R. Chowdhury | A. Havulinna | P. Jousilahti | T. Harris | I. Rudan | D. Boomsma | E. D. de Geus | M. Swertz | D. Porteous | A. Gow | A. Pattie | J. Starr | H. Cordell | N. Wareham | Antti-Pekka Sarin | A. Mahajan | J. Hottenga | J. Ried | C. Nelson | J. Deelen | A. Hamsten | C. V. van Duijn | A. Jula | Xiuqing Guo | C. Tzourio | H. Schmidt | A. Teumer | U. Völker | S. Harris | A. Wright | D. Saleheen | H. Watkins | R. Joehanes | J. Bis | B. Oostra | J. Kooner | E. Bottinger | J. Howson | A. Morgan | G. Davies | D. Liewald | L. Lopez | N. Amin | C. Hayward | P. Joshi | I. Kolčić | O. Polašek | V. Vitart | E. Holliday | M. Kähönen | L. Launer | P. Vollenweider | C. Hartman | J. Marten | A. Campbell | A. Goel | J. Luan | I. Nolte | S. Padmanabhan | A. Robino | R. Scott | P. J. van der Most | H. Warren | Weihua Zhang | Jinghua Zhao | M. Brumat | R. de Mutsert | G. Ehret | E. Evangelou | I. Gandin | He Gao | C. Langenberg | B. Lehne | M. Loh | Y. Milaneschi | N. Poulter | L. Rose | P. Sever | J. Chambers | N. Kato | A. Oldehinkel | P. van der Harst | D. Mook-Kanamori | W. Palmas | A. Morrison | G. Verwoert | B. Keavney | R. Loos | R. Strawbridge | C. Palmer | K. Khaw | Å. Johansson | L. Lyytikäinen | M. Bochud | U. Gyllensten | P. Pramstaller | I. Tzoulaki | J. Jukema | D. Shields | G. Paré | J. Marrugat | M. Dörr | R. Rettig | G. Chauhan | S. Debette | S. Trompet | V. Giedraitis | Yingchang Lu | C. Menni | D. Stott | J. Sundström | N. Verweij | S. Bakker | R. Gansevoort | M. Cocca | F. Drenos | G. Girotto | R. Li-Gao | P. Surendran | P. Knekt | R. Jansen | E. Org | M. Laan | B. Prins | E. Hofer | M. Abedi | Jiang He | S. Thériault | A. Vergnaud | D. Toniolo | H. Riese | C. Batini | M. Traglia | J. Huffman | T. Nutile | M. D. de Borst | C. Cabrera | N. Shah | Chunyu Liu | Andrew A. Hicks | Mattias Frånberg | J. Knight | C. Sala | C. Barbieri | T. Niiranen | M. Ciullo | D. Ruggiero | R. Sorice | D. Vuckovic | D. Siscovick | Ahmad Vaez | Andrew P. Morris | P. Nandakumar | K. Ayers | S. Thom | M. Seelen | R. Scott | Y. Saba | S. Sõber | M. Tomaszewski | L. Lin | Christopher Newton-Cheh | Neil Poulter | Niek Verweij | Rajiv Chowdhury | Cecilia M Lindgren | Peter Sever | Meixia Ren | Ron T Gansevoort | Aldi T Kraja | E Shyong Tai | M. Ren | Patricia B Munroe | Jaspal S Kooner | Maciej Tomaszewski | Joanne Knight | Chrysovalanto Mamasoula | Morris Brown | C. Oldmeadow | A. Erzurumluoglu | Joanna M M Howson | Annette Peters | Chunyu Liu | Helen R Warren | Claudia P Cabrera | James P Cook | Marcelo P Segura Lepe | M Abdullah Said | David Porteous | Maris Alver | John Connell | Georg B Ehret | T. Blake | J. Damman | Peter J. van der Most | J. Knight | F. Mach | M. Larson | J. Yao | C. Lindgren | U. Gyllensten | A. Smith | O. Raitakari | Harry Campbell | A. Johnson | Simon A Thom | Kenneth M. Rice | M. P. S. Lepe | M. A. Said | S. Kathiresan | R. Elosúa | D. Porteous | L. Lind | S. Koskinen | James F. Wilson | Maris Alver | Evangelos A. Evangelou | Franco Giulianini | Paul Elliott | Andrew D. Morris | A. Hofman | R. Schmidt | P. Gasparini | U. Völker | A. Uitterlinden | P. van der harst | T. Spector | Borbála Mifsud | Shih-Jen Hwang | P. O’Reilly | Francis S. Collins | Yusuf Demirkale | Louise V Ahmad Rick Roby Peter J A Mesut Paul Claudia P H Wain Vaez Jansen Joehanes van der Most Erz | Fabiola Del Greco M | Tatijana Zemonik | Michael R Barnes | Quang Tri Nguyen | A. John | Michael R Ioanna Mark J Paul Barnes Tzoulaki Caulfield Elliott | E. Tai | Rodney J. Scott | A. Smith | L. Rose | Weihua Zhang | Rajiv Chowdhury | M. Kähönen | Michela Traglia | M. Said | T. Harris | A. Goel | B. Oostra | F. Collins | François Mach | Michael A. Nalls | Andrew D. Johnson | MartinD. Tobin | Cristina Menni | Roberto Elosua | Alice Stanton | Igor Rudan | Ruth J. F. Loos | Jerome I. Rotter | Alan F. Wright | John M. Starr | B.W.J.H. Penninx | Johan Sundström | A. Palotie | Alan L. James | Robert A. Scott | Olli T. Raitakari | Albert V Smith | Hugh Watkins | A. Jackson | Morris J. Brown | M. Tomaszewski | Colin N. A. Palmer | George B. Ehret | Paul F. O’Reilly | Yongmei Liu | N. Wareham | B. Keavney | Terho Lehtimäki | J. Tuomilehto | Elizabeth G. Holliday | Rodney J. Scott | A. Campbell | P. Elliott | G. Abecasis | Guillaume Paré | Anders Hamsten | Timothy D. Spector | Cecilia M. Lindgren | D. Stott | A. Uitterlinden | Cornelia M. van Duijn | J. Connell | Aravinda Chakravarti | Sarah E. Harris | Andrew P. Morris | Heather J. Cordell | Kenneth M. Rice | R. Gansevoort | Rick Jansen | Andrew D. Morris | A. Peters | Denis C. Shields | Claudia P. Cabrera | C. Newton‐Cheh | R. Elosua | Helena Schmidt | M. Dörr | B. Psaty | Kent D. Taylor | Oscar Franco | Albert V. Smith | Erwin P. Bottinger | Lars Lind | Kristin L. Ayers | Peter J. Munson | Alex S. F. Doney | Nilesh J. Samani | Pekka Jousilahti | P. Vollenweider | David P. Strachan | A. Doney | Paul M. Ridker | Daniel Levy | Antti Jula | Massimo Mangino | Nabi Shah | T. D. Spector | Albert Hofman | Marcus Dörr | Åsa Johansson | Rainer Rettig | Heather J Cordell | Shih-Jen Hwang | Oscar H. Franco | Christopher P. Nelson | J. Marrugat | V. Gudnason | A. Smith | Stephan J. L. Bakker | Michael R Barnes | C. N. Palmer | Sarah H Wild | K. Khaw | P. Sever | Erik Ingelsson | Chunyu Liu | H. Snieder | Norihiro Kato | Neil Poulter | Fabiola Del Greco M | Kristin L Ayers | Tatijana Zemonik | Maryam Abedi | Gail Davies | François Mach | Aude Saint Pierre | C. Tzourio | D. Conen | Attia John | C. M. Lindgren | C. Hartman | Michael R Ioanna Mark J Paul Barnes Tzoulaki Caulfield Elliott | Nilesh J. Samani | B. Penninx | Shih-Jen Hwang | V. Salomaa | T. Lehtimäki | Joanna M. M. Howson | Paolo Gasparini | P. Ridker | J. Starr | J. Zhao | David P Strachan | Jaakko Tuomilehto | Gonçalo R. Abecasis | K. Taylor | I. Deary | J. Jukema | A. D. Morris | Jerome I. Rotter | Xiuqing Guo | J. Luan | Evangelos Evangelou | L. Lin | Neil Poulter | Peter Sever | Bernard D Keavney | Fabiola Del Greco M | Sarah E. Harris | Tatijana Zemonik | Maryam Abedi | Attia John | John Starr | C. V. van Duijn | Michael R Ioanna Mark J Paul Barnes Tzoulaki Caulfield Elliott | Rodney J Scott | Bernard D. Keavney | Fabiola Del Greco M | Tatijana Zemonik | Maryam Abedi | François Mach | Attia John | Michael R Ioanna Mark J Paul Barnes Tzoulaki Caulfield Elliott

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