The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals.
Nature genetics 2015 ; 48: 1171-1184.
Ehret GB, Ferreira T, Chasman DI, Jackson AU, Schmidt EM, Johnson T, Thorleifsson G, Luan J, Kanoni S, Strawbridge RJ, Shungin D, Kaakinen M, Kristiansson K, Kleber ME, Lyytikäinen LP, Eriksson N, Nolte IM, Magnusson PK, Folkersen L, Pers TH, Lataniotis L, Jansen R, Johnson AD, Kim YJ, Zhao W, Tayo BO, Bochud M, Absher D, Adair LS, Amin N, Baldassarre D, Balkau B, Bandinelli S, Barroso I, Bis JC, Bjornsdottir G, Boehnke M, Boerwinkle E, Bonnycastle LL, Boomsma DI, Bornstein SR, Brown MJ, Burnier M, Chambers JC, Cheng CY, Chines PS, Collins FS, Döring A, Danesh J, de Faire U, Delgado G, Dominiczak AF, Doney ASF, Drenos F, Edkins S, Eicher JD, Enroth S, Erdmann J, Eriksson P, Esko T, Fall T, Farrall M, Felix JF, Ferrières J, Ferrucci L, Fornage M, Forrester T, Franceschini N, Franco-Cereceda A, Fraser RM, Gertow K, Gigante B, Giulianini F, Goel A, Goodall AH, Goodarzi MO, Gorski M, Gräßler J, Gudnason V, Gyllensten U, Hallmans G, Hartikainen AL, Hassinen M, Hayward C, Herzig KH, Hicks AA, Hingorani AD, Hirschhorn JN, Hofman A, Holmen OL, Hottenga JJ, Howard P, Hunt SC, Ikram MA, Illig T, Jensen RA, Kähönen M, Kathiresan S, Keating BJ, Khaw KT, Kim YK, Kivimaki M, Klopp N, Kooner JS, Krauss RM, Kutalik Z, Kuusisto J, Lakka TA, Lee NR, Lee IT, Lee WJ, Levy D, Lindström J, Lobbens S, Männistö S, Müller G, Müller-Nurasyid M, Mach F, Marouli E, McCarthy MI, McKenzie CA, Menni C, Metspalu A, Montasser ME, Morris AD, Morrison AC, Mulas A, Nagaraja R, Narisu N, Nikus K, O'Donnell CJ, Ong KK, Palmer CD, Pedersen NL, Penninx BW, Perola M, Peters A, Poulter N, Pramstaller PP, Psaty BM, Quertermous T, Rao DC, Rasheed A, Renstrom F, Rettig R, Rice KM, Roberts R, Rose LM, Samani NJ, Sanna S, Saramies J, Schunkert H, Sebert S, Sheu WH, Smit JH, Smith AV, Spector TD, Stančáková A, Stringham HM, Sundström J, Swift AJ, Syvänen AC, Tai ES, Tanaka T, Teumer A, Thorsteinsdottir U, Tobin MD, Tremoli E, Uitterlinden AG, Uusitupa M, Vaez A, Vaidya D, van Duijn CM, Virtamo J, Vitart V, Voight BF, Vollenweider P, Wain LV, Wareham NJ, Watkins H, Westra HJ, Wilsgaard T, Wilson JF, Wong TY, Yengo L, Zhang W, Zhao JH, Bovet P, Cooper RS, Mohlke KL, Saleheen D, Lee JY, Elliott P, 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, März W, Kumari M, Salomaa V, Chen YI, Rotter JI, Froguel P, Järvelin MR, Kuulasmaa K, Franks PW, Hamsten A, Wichmann HE, Palmer CNA, Stefansson K, Ridker PM, Loos RJF, Chakravarti A, Deloukas P, Morris AP, Munroe PB
DOI : 10.1038/ng.3667
PubMed ID : 27618452
PMCID : NIHMS810971
Abstract
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.