The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals.
Ehret GB., Ferreira T., Chasman DI., Jackson AU., Schmidt EM., Johnson T., Thorleifsson G., Luan J., Donnelly LA., Kanoni S., Petersen A-K., Pihur V., Strawbridge RJ., Shungin D., Hughes MF., Meirelles O., Kaakinen M., Bouatia-Naji N., Kristiansson K., Shah S., Kleber ME., Guo X., Lyytikäinen L-P., Fava C., Eriksson N., Nolte IM., Magnusson PK., Salfati EL., Rallidis LS., Theusch E., Smith AJP., Folkersen L., Witkowska K., Pers TH., Joehanes R., Kim SK., Lataniotis L., Jansen R., Johnson AD., Warren H., Kim YJ., Zhao W., Wu Y., Tayo BO., Bochud M., CHARGE-EchoGen consortium None., CHARGE-HF consortium None., Wellcome Trust Case Control Consortium None., Absher D., Adair LS., Amin N., Arking DE., Axelsson T., Baldassarre D., Balkau B., Bandinelli S., Barnes MR., Barroso I., Bevan S., Bis JC., Bjornsdottir G., Boehnke M., Boerwinkle E., Bonnycastle LL., Boomsma DI., Bornstein SR., Brown MJ., Burnier M., Cabrera CP., Chambers JC., Chang I-S., Cheng C-Y., Chines PS., Chung R-H., Collins FS., Connell JM., Döring A., Dallongeville J., Danesh J., de Faire U., Delgado G., Dominiczak AF., Doney ASF., Drenos F., Edkins S., Eicher JD., Elosua R., Enroth S., Erdmann J., Eriksson P., Esko T., Evangelou E., Evans A., Fall T., Farrall M., Felix JF., Ferrières J., Ferrucci L., Fornage M., Forrester T., Franceschini N., Duran OHF., Franco-Cereceda A., Fraser RM., Ganesh SK., Gao H., Gertow K., Gianfagna F., Gigante B., Giulianini F., Goel A., Goodall AH., Goodarzi MO., Gorski M., Gräßler J., Groves C., Gudnason V., Gyllensten U., Hallmans G., Hartikainen A-L., Hassinen M., Havulinna AS., Hayward C., Hercberg S., Herzig K-H., Hicks AA., Hingorani AD., Hirschhorn JN., Hofman A., Holmen J., Holmen OL., Hottenga J-J., Howard P., Hsiung CA., Hunt SC., Ikram MA., Illig T., Iribarren C., Jensen RA., Kähönen M., Kang H., Kathiresan S., Keating BJ., Khaw K-T., Kim YK., Kim E., Kivimaki M., Klopp N., Kolovou G., Komulainen P., Kooner JS., Kosova G., Krauss RM., Kuh D., Kutalik Z., Kuusisto J., Kvaløy K., Lakka TA., Lee NR., Lee I-T., Lee W-J., Levy D., Li X., Liang K-W., Lin H., Lin L., Lindström J., Lobbens S., Männistö S., Müller G., Müller-Nurasyid M., Mach F., Markus HS., Marouli E., McCarthy MI., McKenzie CA., Meneton P., Menni C., Metspalu A., Mijatovic V., Moilanen L., Montasser ME., Morris AD., Morrison AC., Mulas A., Nagaraja R., Narisu N., Nikus K., O'Donnell CJ., O'Reilly PF., Ong KK., Paccaud F., Palmer CD., Parsa A., Pedersen NL., Penninx BW., Perola M., Peters A., Poulter N., Pramstaller PP., Psaty BM., Quertermous T., Rao DC., Rasheed A., Rayner NWNWR., Renström F., Rettig R., Rice KM., Roberts R., Rose LM., Rossouw J., Samani NJ., Sanna S., Saramies J., Schunkert H., Sebert S., Sheu WH-H., Shin Y-A., Sim X., Smit JH., Smith AV., Sosa MX., Spector TD., Stančáková A., Stanton A., Stirrups KE., Stringham HM., Sundstrom J., Swift AJ., Syvänen A-C., Tai E-S., Tanaka T., Tarasov KV., Teumer A., Thorsteinsdottir U., Tobin MD., Tremoli E., Uitterlinden AG., Uusitupa M., Vaez A., Vaidya D., van Duijn CM., van Iperen EPA., Vasan RS., Verwoert GC., Virtamo J., Vitart V., Voight BF., Vollenweider P., Wagner A., Wain LV., Wareham NJ., Watkins H., Weder AB., Westra H-J., Wilks R., Wilsgaard T., Wilson JF., Wong TY., Yang T-P., Yao J., Yengo L., Zhang W., Zhao JH., Zhu X., Bovet P., Cooper RS., Mohlke KL., Saleheen D., Lee J-Y., Elliott P., Gierman HJ., Willer CJ., Franke L., Hovingh GK., Taylor KD., Dedoussis G., Sever P., Wong A., Lind L., Assimes TL., Njølstad I., Schwarz PE., Langenberg C., Snieder H., Caulfield MJ., Melander O., Laakso M., Saltevo J., Rauramaa R., Tuomilehto J., Ingelsson E., Lehtimäki T., Hveem K., Palmas W., März W., Kumari M., Salomaa V., Chen Y-DI., Rotter JI., Froguel P., Jarvelin M-R., Lakatta EG., Kuulasmaa K., Franks PW., Hamsten A., Wichmann H-E., Palmer CNA., Stefansson K., Ridker PM., Loos RJF., Chakravarti A., Deloukas P., Morris AP., Newton-Cheh C., Munroe PB.
To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure-related pathways and highlight tissues beyond the classical renal system in blood pressure regulation.