Journal
AMERICAN JOURNAL OF HUMAN GENETICS
Volume 94, Issue 3, Pages 349-360Publisher
CELL PRESS
DOI: 10.1016/j.ajhg.2013.12.016
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Funding
- MRC [MC_UU_12013/8, G0802432, G0902313, MC_UU_12013/1, MR/K013351/1, G9521010] Funding Source: UKRI
- British Heart Foundation [PG/07/085/23349, SP/08/002/24118, FS/12/33/29561, FS/11/35/28871, FS/12/8/29377, PG/09/022/26739, FS/14/12/30540] Funding Source: researchfish
- Medical Research Council [MC_UU_12013/8, MC_UU_12013/1, G0902313, MR/K006584/1, G0802432, MR/K013351/1, G9521010] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0512-10052, NF-SI-0508-10116, NF-SI-0513-10059, NF-SI-0512-10113] Funding Source: researchfish
- British Heart Foundation [FS/11/35/28871, FS/12/33/29561, FS/14/12/30540, PG/07/085/23349, PG/09/022/26739, FS/12/8/29377, SP/08/002/24118] Funding Source: Medline
- Medical Research Council [MC_UU_12013/1, G0802432, MR/K013351/1, MR/K006584/1, MC_UU_12013/8, G9521010, G0902313] Funding Source: Medline
- NCATS NIH HHS [UL1 TR000124, UL1 TR000064] Funding Source: Medline
- NHLBI NIH HHS [R01 HL074730, R01 HL088120] Funding Source: Medline
- NIA NIH HHS [R37 AG011099, R01 AG016592, R01 AG021917] Funding Source: Medline
- NIDDK NIH HHS [P30 DK063491, P30 DK072488] Funding Source: Medline
- NIGMS NIH HHS [U01 GM074492] Funding Source: Medline
- NLM NIH HHS [T15 LM007033] Funding Source: Medline
- Wellcome Trust [090532] Funding Source: Medline
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Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped similar to 50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry. Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p < 6 x 10(-7)) and confirmed 27 previously reported associations. Bioinformatic analysis of the 11 loci provided support for a putative role in hypertension of several genes, such as CDK6 and NUCB2. Analysis of potential pharmacological targets in databases of small molecules showed that ten of the genes are predicted to be a target for small molecules. In summary, we identified previously unknown loci associated with BP. Our findings extend our understanding of genes involved in BP regulation, which may provide new targets for therapeutic intervention or drug response stratification.
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