Journal
NATURE GENETICS
Volume 48, Issue 10, Pages 1151-1161Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.3654
Keywords
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Categories
Funding
- Biotechnology and Biological Sciences Research Council Funding Source: Medline
- British Heart Foundation [SP/08/005/25115, SP/04/002, RG/14/5/30893, SP/09/002, PG/02/128, RG/15/15/31742, FS/14/66/31293, RG/07/005/23633, SP/10/6/28562] Funding Source: Medline
- Medical Research Council [G0902313, G1002319, MC_UU_00002/7, MC_UU_12013/5, MC_U106179471, G0600237, G0802782, G0700931, MR/K006584/1, MR/L01341X/1, MR/K026992/1, G0800270, G0000934, G0601966, G0600705, G0500539, MC_PC_U127561128, G9521010D, MC_UU_12015/1] Funding Source: Medline
- NCI NIH HHS [HHSN261200800001E] Funding Source: Medline
- NHGRI NIH HHS [Z01 HG000024] Funding Source: Medline
- NHLBI NIH HHS [HHSN268201000029C, T32 HL007055, R01 HL127564, K99 HL094535, R01 HL107816, R01 HL087679, R01 HL109946] Funding Source: Medline
- NICHD NIH HHS [R01 HD057194] Funding Source: Medline
- NIDA NIH HHS [R01 DA006227] Funding Source: Medline
- NIDDK NIH HHS [U01 DK085524, U01 DK085545, U01 DK085526, R01 DK093757, U01 DK062370, P30 DK020595, P30 DK020572, RC2 DK088389, U01 DK085584, U01 DK085501, R01 DK072193] Funding Source: Medline
- NIMH NIH HHS [R01 MH063706, R01 MH101822, R01 MH101810, RL1 MH083268] Funding Source: Medline
- NLM NIH HHS [R01 LM010098] Funding Source: Medline
- Wellcome Trust [WT098381, 083948, 100114, WT098017, 068545/Z/02, 084723/Z/08/Z, 085475, 098051, 086596/Z/08/Z, WT091310] Funding Source: Medline
- Chief Scientist Office [CZD/16/6/4] Funding Source: Medline
- Wellcome Trust [086596/Z/08/Z] Funding Source: Wellcome Trust
- British Heart Foundation [RG/13/13/30194, RG/08/014/24067, RG/14/5/30893, SP/10/6/28562, RG/15/15/31742] Funding Source: researchfish
- Chief Scientist Office [CZD/16/6/4] Funding Source: researchfish
- Lundbeck Foundation [R165-2013-15410] Funding Source: researchfish
- Medical Research Council [1241993, MR/K026992/1, G0700931, MR/L01341X/1, MC_U106179471, MR/N01104X/1, 1646420, G1002319, G0601966, MR/K006584/1, G0600237, MC_UU_12013/5, MC_UU_12013/1, MC_UU_12013/3, MR/L003120/1, G0600705, MC_UU_12015/1, MC_PC_U127561128, G0800270, G0802782, G0902313, G1001799] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0507-10267, NF-SI-0512-10052, NF-SI-0513-10059, NF-SI-0512-10019, NF-SI-0512-10113, NF-SI-0512-10165, NF-SI-0611-10136, NF-SI-0514-10027, NF-SI-0611-10099, NF-SI-0507-10228] Funding Source: researchfish
- Novo Nordisk Fonden [NNF15OC0016362, NNF12OC1016374] Funding Source: researchfish
- MRC [G0601966, G1001799, MR/L003120/1, MC_UU_12013/3, MC_UU_12013/1, MC_PC_U127561128, G0902313, G0600705, MR/N01104X/1, G1002319, MR/L01341X/1, G0700931, MC_UU_12015/1, G0600237, G0800270, MC_UU_12013/5, G0802782] Funding Source: UKRI
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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 similar to 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.
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