Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.

Evangelou E1,2, Warren HR3,4, Mosen-Ansorena D1, Mifsud B3, Pazoki R1, Gao H1,5, Ntritsos G2, Dimou N2, Cabrera CP3,4, Karaman I1, Ng FL3, Evangelou M1,6, Witkowska K3, Tzanis E3, Hellwege JN7, Giri A8, Velez Edwards DR8, Sun YV9,10, Cho K11,12, Gaziano JM11,12, Wilson PWF13, Tsao PS14, Kovesdy CP15, Esko T16,17, Mägi R16, Milani L16, Almgren P18, Boutin T19, Debette S20,21, Ding J22, Giulianini F23, Holliday EG24, Jackson AU25, Li-Gao R26, Lin WY27, Luan J28, Mangino M29,30, Oldmeadow C24, Prins BP31, Qian Y22, Sargurupremraj M21, Shah N32,33, Surendran P27, Thériault S34,35, Verweij N17,36,37, Willems SM28, Zhao JH28, Amouyel P38, Connell J39, de Mutsert R26, Doney ASF32, Farrall M40,41, Menni C29, Morris AD42, Noordam R43, Paré G34, Poulter NR44, Shields DC45, Stanton A46, Thom S47, Abecasis G48, Amin N49, Arking DE50, Ayers KL51,52, Barbieri CM53, Batini C54, Bis JC55, Blake T54, Bochud M56, Boehnke M25, Boerwinkle E57, Boomsma DI58, Bottinger EP59, Braund PS60,61, Brumat M62, Campbell A63,64, Campbell H65, Chakravarti A50, Chambers JC1,5,66,67,68, Chauhan G69, Ciullo M70,71, Cocca M72, Collins F73, Cordell HJ51, Davies G74,75, Borst MH76, Geus EJ58, Deary IJ74,75, Deelen J77, Del Greco M F78, Demirkale CY79, Dörr M80,81, Ehret GB50,82, Elosua R83,84, Enroth S85, Erzurumluoglu AM54, Ferreira T86,87, Frånberg M88,89,90, Franco OH91, Gandin I62, Gasparini P62,72, Giedraitis V92, Gieger C93,94,95, Girotto G62,72, Goel A40,41, Gow AJ74,96, Gudnason V97,98, Guo X99, Gyllensten U85, Hamsten A88,89, Harris TB100, Harris SE63,74, Hartman CA101, Havulinna AS102,103, Hicks AA78, Hofer E104,105, Hofman A91,106, Hottenga JJ58, Huffman JE19,107,108, Hwang SJ107,108, Ingelsson E109,110, James A111,112, Jansen R113, Jarvelin MR1,5,114,115,116, Joehanes R107,117, Johansson Å85, Johnson AD107,118, Joshi PK65, Jousilahti P102, Jukema JW119, Jula A102, Kähönen M120,121, Kathiresan S17,36,122, Keavney BD123,124, Khaw KT125, Knekt P102, Knight J126, Kolcic I127, Kooner JS5,67,68,128, Koskinen S102, Kristiansson K102, Kutalik Z56,129, Laan M130, Larson M107, Launer LJ100, Lehne B1, Lehtimäki T131,132, Liewald DCM74,75, Lin L82, Lind L133, Lindgren CM40,87,134, Liu Y135, Loos RJF28,59,136, Lopez LM74,137,138, Lu Y59, Lyytikäinen LP131,132, Mahajan A40, Mamasoula C139, Marrugat J83, Marten J19, Milaneschi Y140, Morgan A62, Morris AP40,141, Morrison AC142, Munson PJ79, Nalls MA143,144, Nandakumar P50, Nelson CP60,61, Niiranen T102,145, Nolte IM146, Nutile T70, Oldehinkel AJ147, Oostra BA49, O'Reilly PF148, Org E16, Padmanabhan S64,149, Palmas W150, Palotie A103,151,152, Pattie A75, Penninx BWJH140, Perola M102,103,153, Peters A94,95,154, Polasek O127,155, Pramstaller PP78,156,157, Nguyen QT79, Raitakari OT158,159, Ren M160, Rettig R161, Rice K162, Ridker PM23,163, Ried JS94, Riese H147, Ripatti S103,164, Robino A72, Rose LM23, Rotter JI99, Rudan I65, Ruggiero D70,71, Saba Y165, Sala CF53, Salomaa V102, Samani NJ60,61, Sarin AP103, Schmidt R104, Schmidt H165, Shrine N54, Siscovick D166, Smith AV97,98, Snieder H146, Sõber S130, Sorice R70, Starr JM74,167, Stott DJ168, Strachan DP169, Strawbridge RJ88,89, Sundström J133, Swertz MA170, Taylor KD99, Teumer A81,171, Tobin MD54, Tomaszewski M123,124, Toniolo D53, Traglia M53, Trompet S119,172, Tuomilehto J173,174,175,176, Tzourio C21, Uitterlinden AG91,177, Vaez A146,178, van der Most PJ146, van Duijn CM49, Vergnaud AC1, Verwoert GC91, Vitart V19, Völker U81,179, Vollenweider P180, Vuckovic D62,181, Watkins H40,41, Wild SH182, Willemsen G58, Wilson JF19,65, Wright AF19, Yao J99, Zemunik T183, Zhang W1,67, Attia JR24, Butterworth AS27,184, Chasman DI23,163, Conen D185,186, Cucca F187,188, Danesh J27,184, Hayward C19, Howson JMM27, Laakso M189, Lakatta EG190, Langenberg C28, Melander O18, Mook-Kanamori DO26,191, Palmer CNA32, Risch L192,193,194, Scott RA28, Scott RJ24, Sever P128, Spector TD29, van der Harst P195, Wareham NJ28, Zeggini E31, Levy D107,118, Munroe PB3,4, Newton-Cheh C134,196,197, Brown MJ3,4, Metspalu A16, Hung AM198, O'Donnell CJ199, Edwards TL7; Million Veteran Program, Psaty BM200,201, Tzoulaki I1,2,5, Barnes MR3,4, Wain LV54,61, Elliott P202,203,204,205,206, Caulfield MJ207,208.

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Abstract

High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.