TY - JOUR
T1 - Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension
AU - Surendran, Praveen
AU - Drenos, Fotios
AU - Young, Robin
AU - Warren, Helen
AU - Cook, James P
AU - Manning, Alisa K
AU - Grarup, Niels
AU - Sim, Xueling
AU - Barnes, Daniel R
AU - Witkowska, Kate
AU - Staley, James R
AU - Tragante, Vinicius
AU - Tukiainen, Taru
AU - Yaghootkar, Hanieh
AU - Masca, Nicholas
AU - Freitag, Daniel F
AU - Ferreira, Teresa
AU - Giannakopoulou, Olga
AU - Tinker, Andrew
AU - Harakalova, Magdalena
AU - Mihailov, Evelin
AU - Liu, Chunyu
AU - Kraja, Aldi T
AU - Nielsen, Sune Fallgaard
AU - Rasheed, Asif
AU - Samuel, Maria
AU - Zhao, Wei
AU - Bonnycastle, Lori L
AU - Jackson, Anne U
AU - Narisu, Narisu
AU - Swift, Amy J
AU - Southam, Lorraine
AU - Marten, Jonathan
AU - Huyghe, Jeroen R
AU - Stančáková, Alena
AU - Fava, Cristiano
AU - Ohlsson, Therese
AU - Matchan, Angela
AU - Stirrups, Kathleen E
AU - Bork-Jensen, Jette
AU - Gjesing, Anette P
AU - Kontto, Jukka
AU - Perola, Markus
AU - Shaw-Hawkins, Susan
AU - Havulinna, Aki S
AU - Zhang, He
AU - Donnelly, Louise A
AU - Groves, Christopher J
AU - Menni, Cristina
AU - Spector, Timothy D
AU - CHARGE-Heart Failure Consortium
AU - METASTROKE Consortium
AU - GIANT Consortium
AU - EPIC-InterAct Consortium
AU - LifeLines Cohort Study
AU - Wellcome Trust Case Control Consortium
AU - Understanding Society Scientific Group
AU - EPIC-CVD Consortium
AU - CHARGE+ Exome Chip Blood Pressure Consortium
AU - T2D-GENES Consortium
AU - GoT2DGenes Consortium
AU - Exome-BP Consortium
AU - CHD Exome+ Consortium
PY - 2016/10
Y1 - 2016/10
N2 - High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used ∼155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.
AB - High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used ∼155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.
KW - Journal Article
U2 - 10.1038/ng.3654
DO - 10.1038/ng.3654
M3 - Article
C2 - 27618447
SN - 1061-4036
VL - 48
SP - 1151
EP - 1161
JO - Nature Genetics
JF - Nature Genetics
IS - 10
ER -
