The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

TY - JOUR

T1 - The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

AU - CHARGE-EchoGen Consortium

AU - CHARGE-HF Consortium

AU - Wellcome Trust Case Control Consortium

AU - Ehret, Georg B.

AU - Ferreira, Teresa

AU - Chasman, Daniel I.

AU - Jackson, Anne U.

AU - Schmidt, Ellen M.

AU - Johnson, Toby

AU - Thorleifsson, Gudmar

AU - Luan, Jian'an

AU - Donnelly, Louise A.

AU - Kanoni, Stavroula

AU - Petersen, Ann-Kristin

AU - Pihur, Vasyl

AU - Strawbridge, Rona J.

AU - Shungin, Dmitry

AU - Hughes, Maria F.

AU - Meirelles, Osorio

AU - Kaakinen, Marika

AU - Bouatia-Naji, Nabila

AU - Kristiansson, Kati

AU - Shah, Sonia

AU - Kleber, Marcus E.

AU - Guo, Xiuqing

AU - Lyytikäinen, Leo-Pekka

AU - Fava, Cristiano

AU - Eriksson, Niclas

AU - Nolte, Ilja M.

AU - Magnusson, Patrik K.

AU - Salfati, Elias L.

AU - Rallidis, Loukianos S.

AU - Theusch, Elizabeth

AU - Smith, Andrew J. P.

AU - Folkersen, Lasse

AU - Witkowska, Kate

AU - Pers, Tune H.

AU - Joehanes, Roby

AU - Kim, Stuart K.

AU - Lataniotis, Lazaros

AU - Jansen, Rick

AU - Johnson, Andrew D.

AU - Warren, Helen

AU - Kim, Young Jin

AU - Zhao, Wei

AU - Wu, Ying

AU - Tayo, Bamidele O.

AU - Bochud, Murielle

AU - Absher, Devin

AU - Connell, John M.

AU - Doney, Alex S. F.

AU - Morris, Andrew D.

AU - Palmer, Colin N. A.

AU - Newton-Cheh, Christopher

AU - Munroe, Patricia B.

PY - 2016/10

Y1 - 2016/10

N2 - 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.

AB - 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.

KW - Genome-wide association studies

KW - Hypertension

UR - https://ora.ox.ac.uk/objects/uuid:af680707-f9c2-44b5-9be6-9db160a9ba5d

U2 - 10.1038/ng.3667

DO - 10.1038/ng.3667

M3 - Article

C2 - 27618452

SN - 1061-4036

VL - 48

SP - 1171

EP - 1184

JO - Nature Genetics

JF - Nature Genetics

ER -