Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.
International Consortium for Blood Pressure Genome-Wide Association Studies None., Ehret GB., Munroe PB., Rice KM., Bochud M., Johnson AD., Chasman DI., Smith AV., Tobin MD., Verwoert GC., Hwang S-J., Pihur V., Vollenweider P., O'Reilly PF., Amin N., Bragg-Gresham JL., Teumer A., Glazer NL., Launer L., Zhao JH., Aulchenko Y., Heath S., Sõber S., Parsa A., Luan J., Arora P., Dehghan A., Zhang F., Lucas G., Hicks AA., Jackson AU., Peden JF., Tanaka T., Wild SH., Rudan I., Igl W., Milaneschi Y., Parker AN., Fava C., Chambers JC., Fox ER., Kumari M., Go MJ., van der Harst P., Kao WHL., Sjögren M., Vinay DG., Alexander M., Tabara Y., Shaw-Hawkins S., Whincup PH., Liu Y., Shi G., Kuusisto J., Tayo B., Seielstad M., Sim X., Nguyen K-DH., Lehtimäki T., Matullo G., Wu Y., Gaunt TR., Onland-Moret NC., Cooper MN., Platou CGP., Org E., Org E., Hardy R., Dahgam S., Palmen J., Vitart V., Braund PS., Kuznetsova T., Uiterwaal CSPM., Adeyemo A., Palmas W., Campbell H., Ludwig B., Tomaszewski M., Tzoulaki I., Palmer ND., CARDIoGRAM consortium None., CKDGen Consortium None., KidneyGen Consortium None., EchoGen consortium None., CHARGE-HF consortium None., Aspelund T., Garcia M., Chang Y-PC., O'Connell JR., Steinle NI., Grobbee DE., Arking DE., Kardia SL., Morrison AC., Hernandez D., Najjar S., McArdle WL., Hadley D., Brown MJ., Connell JM., Hingorani AD., Day INM., Lawlor DA., Beilby JP., Lawrence RW., Clarke R., Hopewell JC., Ongen H., Dreisbach AW., Li Y., Young JH., Bis JC., Kähönen M., Viikari J., Adair LS., Lee NR., Chen M-H., Olden M., Pattaro C., Bolton JAH., Köttgen A., Bergmann S., Mooser V., Chaturvedi N., Frayling TM., Islam M., Jafar TH., Erdmann J., Kulkarni SR., Bornstein SR., Grässler J., Groop L., Voight BF., Kettunen J., Howard P., Taylor A., Guarrera S., Ricceri F., Emilsson V., Plump A., Barroso I., Khaw K-T., Weder AB., Hunt SC., Sun YV., Bergman RN., Collins FS., Bonnycastle LL., Scott LJ., Stringham HM., Peltonen L., Perola M., Vartiainen E., Brand S-M., Staessen JA., Wang TJ., Burton PR., Soler Artigas M., Dong Y., Snieder H., Wang X., Zhu H., Lohman KK., Rudock ME., Heckbert SR., Smith NL., Wiggins KL., Doumatey A., Shriner D., Veldre G., Viigimaa M., Kinra S., Prabhakaran D., Tripathy V., Langefeld CD., Rosengren A., Thelle DS., Corsi AM., Singleton A., Forrester T., Hilton G., McKenzie CA., Salako T., Iwai N., Kita Y., Ogihara T., Ohkubo T., Okamura T., Ueshima H., Umemura S., Eyheramendy S., Meitinger T., Wichmann H-E., Cho YS., Kim H-L., Lee J-Y., Scott J., Sehmi JS., Zhang W., Hedblad B., Nilsson P., Smith GD., Wong A., Narisu N., Stančáková A., Raffel LJ., Yao J., Kathiresan S., O'Donnell CJ., Schwartz SM., Ikram MA., Longstreth WT., Mosley TH., Seshadri S., Shrine NRG., Wain LV., Morken MA., Swift AJ., Laitinen J., Prokopenko I., Zitting P., Cooper JA., Humphries SE., Danesh J., Rasheed A., Goel A., Hamsten A., Watkins H., Bakker SJL., van Gilst WH., Janipalli CS., Mani KR., Yajnik CS., Hofman A., Mattace-Raso FUS., Oostra BA., Demirkan A., Isaacs A., Rivadeneira F., Lakatta EG., Orru M., Scuteri A., Ala-Korpela M., Kangas AJ., Lyytikäinen L-P., Soininen P., Tukiainen T., Würtz P., Ong RT-H., Dörr M., Kroemer HK., Völker U., Völzke H., Galan P., Hercberg S., Lathrop M., Zelenika D., Deloukas P., Mangino M., Spector TD., Zhai G., Meschia JF., Nalls MA., Sharma P., Terzic J., Kumar MVK., Denniff M., Zukowska-Szczechowska E., Wagenknecht LE., Fowkes FGR., Charchar FJ., Schwarz PEH., Hayward C., Guo X., Rotimi C., Bots ML., Brand E., Samani NJ., Polasek O., Talmud PJ., Nyberg F., Kuh D., Laan M., Hveem K., Palmer LJ., van der Schouw YT., Casas JP., Mohlke KL., Vineis P., Raitakari O., Ganesh SK., Wong TY., Tai ES., Cooper RS., Laakso M., Rao DC., Harris TB., Morris RW., Dominiczak AF., Kivimaki M., Marmot MG., Miki T., Saleheen D., Chandak GR., Coresh J., Navis G., Salomaa V., Han B-G., Zhu X., Kooner JS., Melander O., Ridker PM., Bandinelli S., Gyllensten UB., Wright AF., Wilson JF., Ferrucci L., Farrall M., Tuomilehto J., Pramstaller PP., Elosua R., Soranzo N., Sijbrands EJG., Altshuler D., Loos RJF., Shuldiner AR., Gieger C., Meneton P., Uitterlinden AG., Wareham NJ., Gudnason V., Rotter JI., Rettig R., Uda M., Strachan DP., Witteman JCM., Hartikainen A-L., Beckmann JS., Boerwinkle E., Vasan RS., Boehnke M., Larson MG., Järvelin M-R., Psaty BM., Abecasis GR., Chakravarti A., Elliott P., van Duijn CM., Newton-Cheh C., Levy D., Caulfield MJ., Johnson T.
Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.