Journal
NATURE GENETICS
Volume 48, Issue 10, Pages 1171-1184Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.3667
Keywords
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Categories
Funding
- British Heart Foundation [RG/10/12/28456, FS/13/6/29977, RG/13/2/30098, RG/14/5/30893, SP/10/6/28562] Funding Source: researchfish
- Lundbeck Foundation [R190-2014-3904] Funding Source: researchfish
- Medical Research Council [MC_UU_12015/1, G0601261, MC_UU_12015/2, MR/N003284/1, MR/K006584/1, G0401527, MC_UU_12013/3, G0600705, MC_UU_12013/5, G0700931, G1000143, MC_PC_U127561128, MC_UU_12019/1, G0601966, G1002319, MR/L01341X/1, MC_CF023241, MR/K013351/1, MR/N005813/1, MC_U106179472, G0600237] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0512-10052, NF-SI-0611-10170, NF-SI-0514-10027, NF-SI-0507-10228, NF-SI-0515-10091, NF-SI-0512-10019, NF-SI-0513-10059, NF-SI-0512-10114, NF-SI-0512-10113, NF-SI-0507-10267] Funding Source: researchfish
- NNF Center for Basic Metabolic Research [Pers Group] Funding Source: researchfish
- MRC [MC_U106179472, MR/L003120/1, MR/K013351/1, MC_UU_12013/3, MC_PC_U127561128, MC_UU_12015/2, MC_UU_12019/1, MR/N015746/1, MR/N005813/1, G0600705, G1002319, MR/L01341X/1, G0700931, MC_UU_12015/1, G0600237, G0601261, MR/N003284/1, MC_UU_12013/5, G0601966] Funding Source: UKRI
- Arthritis Research UK Funding Source: Medline
- British Heart Foundation [RG/13/13/30194, PG/02/128, SP/04/002, SP/10/6/28562, SP/08/005/25115, RG/14/5/30893, RG/13/2/30098, RG2008/014, FS/13/6/29977, RG08/008, RG/07/005/23633, RG/10/12/28456] Funding Source: Medline
- FIC NIH HHS [R01 TW005596, R01 TW008288, RC1 TW008485] Funding Source: Medline
- Medical Research Council [G0601966, MC_UU_12019/1, MR/N015746/1, G1002319, MR/L003120/1, G9521010D, G0401527, MR/L01341X/1, G0500539, G0601261, G0000934, MR/K013351/1, MC_UU_12013/5, G1000143, MC_UU_12015/1, MR/K006584/1, G0700931, G0600705, 85374, G0600237, MC_PC_U127561128, MR/N003284/1] Funding Source: Medline
- NCATS NIH HHS [UL1 TR000124] Funding Source: Medline
- NCI NIH HHS [UM1 CA182913] Funding Source: Medline
- NCRR NIH HHS [U54 RR020278, M01 RR016500, M01 RR000425, UL1 RR025774, M01 RR010284, UL1 RR024156, UL1 RR025005, UL1 RR024975, UL1 RR033176, M01 RR000052, P20 RR020649] Funding Source: Medline
- NEI NIH HHS [ZIA EY000401, R01 EY014684, R01 EY018246] Funding Source: Medline
- NHGRI NIH HHS [U01 HG007416, N01HG65403, Z01 HG000024, Z01 HG200362, U01 HG004402, HHSN268200782096C] Funding Source: Medline
- NHLBI NIH HHS [N01HC55020, N01HC85080, R01 HL087647, R01 HL088119, N01HC95169, N01 HC055019, R01 HL087698, N01HC85082, R01 HL087660, HHSN268201100008C, R01 HL109512, R01 HL074166, R01 HL098283, U01 HL054497, R01 HL077477, R21 HL123677, N01 HC055018, N01HC95164, U01 HL054471, N01 HC035129, N01 HC045204, HHSN268201100005C, U01 HL069757, R01 HL059684, R01 HL105756, R01 HL080467, N01HC25195, K24 HL004334, R01 HL043851, N01 HC085085, K23 HL080025, U01 HL084756, N01 HC085084, R01 HL113933, N01HC95160, HHSN268201100010C, RC2 HL101834, U01 HL096917, R01 HL036310, N01 WH42114, R01 HL086694, R01 HL055673, U01 HL054495, N01HC85079, R01 HL080295, N01HC55021, N01 HC095095, R01 HL059367, N01HC95167, N01HC85083, N01 HC045133, R01 HL046380, N01HC95159, N01HC95163, N01HC85086, T32 HL098049, N01 HC015103, K99 HL094535, N01HC55222, R01 HL053353, N01WH32102, HHSN268201100012C, N01HC75150, N01HC95165, T32 HL007208, R01 HL093029, R01 HL085144, U01 HL054473, U01 HL054509, R01 HL109946, N01HC85081, N01 HC045205, N01HC55016, R01 HL093328, N01 HC045134, R01 HL075366, U01 HL072518, R01 HL071025, U01 HL072515, N01HC95168, HHSN268201100006C, U01 HL054496, R01 HL103612, HHSN268201100011C, N01 HC055015, R01 HL122684, N01HC95166, HHSN268201200036C, N01 HC005187, N01HC65226, RC1 HL100245, R01 HL087652, R01 HL087679, R01 HL085251, N02HL64278, HHSN268201100009C, HHSN268201100007C, N01HC95161, U01 HL080295, N01 HC048050, N01 HC048049, R01 HL087641, N01HC95162, R01 HL120393, N01 HC048048, N01 HC048047, U01 HL054472, T32 HL007902] Funding Source: Medline
- NIA NIH HHS [T32 AG000219, N01AG12109, N01 AG062106, R01 AG032098, R01 AG018728, R01 AG015928, R01 AG016592, N01 AG062103, ZIA AG007380, R01 AG025941, R01 AG013196, R01 AG020098, R01 AG027058, Z01 AG000513, HHSN271201200022C, R01 AG010175, R01 AG023629, N01 AG062101, N01 AG012100, R01 AG028555] Funding Source: Medline
- NICHD NIH HHS [P2C HD050924, R03 HD061437, R03 HD062783] Funding Source: Medline
- NIDDK NIH HHS [R01 DK101478, U01 DK062370, R01 DK054261, R01 DK093757, R01 DK078150, R01 DK072193, P60 DK079637, P30 DK072488, P30 DK056350, R01 DK079888, P30 DK063491, R01 DK084350, P30 DK020572, R01 DK062370] Funding Source: Medline
- NIEHS NIH HHS [P30 ES010126, P30 ES007033] Funding Source: Medline
- NIGMS NIH HHS [S06 GM008016, U01 GM074518] Funding Source: Medline
- NIH HHS [N01 WH42124] Funding Source: Medline
- NIMH NIH HHS [RL1 MH083268, RC2 MH089951, R01 MH063706] Funding Source: Medline
- NINDS NIH HHS [U01 NS041588, R21 NS064908] Funding Source: Medline
- Wellcome Trust [085475/B/08/Z, 098051, 090532/Z/09/Z, WT098017, 081917/Z/07/Z, 084723/Z/08/Z, 068545/Z/02] Funding Source: Medline
- Chief Scientist Office Funding Source: Medline
- WHI NIH HHS [N01WH32112, N01 WH042121, N01WH32101, N01WH42108, N01 WH042130, N01WH32109, N01 WH042110, N01WH32100, N01 WH042118, N01 WH042123, N01 WH042129, N01WH32113, N01 WH032122, N01WH22110, N01WH24152, N01 WH042119, N01 WH044221, N01 WH042117, N01 WH042131, N01WH32111, N01 WH032105, N01 WH042111, N01 WH042112, N01WH32108, N01 WH032118, N01 WH042125, N01 WH042115, N01 WH042126, N01WH42113, N01 WH042116, N01 WH042109, N01WH32106, N01 WH032119, N01WH32115, N01 WH042122, N01 WH042132, N01 WH042120, N01 WH042107] Funding Source: Medline
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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.
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