Journal
NATURE GENETICS
Volume 48, Issue 10, Pages 1162-1170Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.3660
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Funding
- British Heart Foundation [RG/14/5/30893] Funding Source: Medline
- Medical Research Council [G0800270, MC_UU_12013/5] Funding Source: Medline
- NCATS NIH HHS [UL1 TR000445, UL1 TR000124] Funding Source: Medline
- NCI NIH HHS [R01 CA047988, UM1 CA182913] Funding Source: Medline
- NCRR NIH HHS [UL1 RR024156] Funding Source: Medline
- NHGRI NIH HHS [U01 HG004603, U01 HG004729] Funding Source: Medline
- NHLBI NIH HHS [R01 HL120393, N01HC95161, HHSN268201100008C, R01 HL068986, HHSN268201300026C, N01HC95169, R01 HL103612, RC2 HL102419, HHSN268201300049C, HHSN268201100012C, N01HC85082, R01 HL080295, HHSN268201200036C, HHSN268201100010C, N01HC85081, N01 HC095159, N01HC85080, N01HC95160, HHSN268201300050C, HHSN268201300029C, R01 HL117078, N01 HC085079, R21 HL121429, N01HC95166, HHSN268201300046C, N02HL64278, HHSN268201100005C, N01HC85083, HHSN268201100009C, N01HC95164, R01 HL080467, R01 HL043851, R01 HL084099, HHSN268201300048C, N01HC95163, HHSN268200900041C, N01HC95167, HHSN268201100006C, HHSN268201300027C, N01HC95165, T32 HL007208, U01 HL130114, HHSN268201100007C, HHSN268200800007C, N01HC95168, N01 HC025195, HHSN268201100011C, HHSN268201300047C, R01 HL087652, N01HC95162, N01HC55222, R01 HL093029, N01HC85086, R01 HL105756, R01 HL071205] Funding Source: Medline
- NIA NIH HHS [HHSN268201300028C, N01 AG062106, RC4 AG039029, R01 AG032098, HHSN271201100004C, U01 AG009740, N01 AG062103, N01AG12100, R01 AG023629, N01 AG062101, RC2 AG036495, HHSN268201300025C, R03 AG046389] Funding Source: Medline
- NIDA NIH HHS [HHSN271201200022C] Funding Source: Medline
- NIDDK NIH HHS [R01 DK089256, P30 DK063491, R01 DK078616, K24 DK080140] Funding Source: Medline
- NIEHS NIH HHS [P30 ES010126] Funding Source: Medline
- NIGMS NIH HHS [R25 GM062459, RC2 GM092618] Funding Source: Medline
- NIH HHS [S10 OD018522, S10 OD020069] Funding Source: Medline
- WHI NIH HHS [HHSN268201100002C, HHSN268201100001C, HHSN268201100004C, HHSN268201100003C] Funding Source: Medline
- British Heart Foundation [RG/14/5/30893, RG/08/014/24067, RG/13/13/30194] Funding Source: researchfish
- Medical Research Council [MR/L003120/1, MC_UU_12013/1, MC_UU_12013/5, G0800270] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0512-10165] Funding Source: researchfish
- MRC [MR/L003120/1, MC_UU_12013/1, G0800270, MC_UU_12013/5] Funding Source: UKRI
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Meta-analyses of association results for blood pressure using exome-centric single-variant and gene-based tests identified 31 new loci in a discovery stage among 146,562 individuals, with follow-up and meta-analysis in 180,726 additional individuals (total n = 327,288). These blood pressure-associated loci are enriched for known variants for cardiometabolic traits. Associations were also observed for the aggregation of rare and low-frequency missense variants in three genes, NPR1, DBH, and PTPMT1. In addition, blood pressure associations at 39 previously reported loci were confirmed. The identified variants implicate biological pathways related to cardiometabolic traits, vascular function, and development. Several new variants are inferred to have roles in transcription or as hubs in protein-protein interaction networks. Genetic risk scores constructed from the identified variants were strongly associated with coronary disease and myocardial infarction. This large collection of blood pressure-associated loci suggests new therapeutic strategies for hypertension, emphasizing a link with cardiometabolic risk.
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