DESCRIPTION:

List of positional candidate genes after correcting for multiple testing and controlling the false discovery rate from genome wide association studies (GWAS) retrieved from the NHGRI-EBI Catalog of published genome-wide association studies (http://www.ebi.ac.uk/gwas/). The disease/trait examined in this study, as reported by the authors, was Hypertension. The EFO term hypertension was annotated to this set after curation by NHGRI-EBI. Intergenic SNPS were mapped to both the upstream and downstream gene. P-value uploaded. This gene set was generated using gwas2gs v. 0.1.8 and the GWAS Catalog v. 1.0.1.

LABEL:

GWAS: hypertension

SCORE TYPE:

P-Value

DATE ADDED:

2017-05-02

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

S Padmanabhan, O Melander, T Johnson, AM Di Blasio, WK Lee, D Gentilini, CE Hastie, C Menni, MC Monti, C Delles, S Laing, B Corso, G Navis, AJ Kwakernaak, P van der Harst, M Bochud, M Maillard, M Burnier, T Hedner, S Kjeldsen, B Wahlstrand, M Sjögren, C Fava, M Montagnana, E Danese, O Torffvit, B Hedblad, H Snieder, JM Connell, M Brown, NJ Samani, M Farrall, G Cesana, G Mancia, S Signorini, G Grassi, S Eyheramendy, HE Wichmann, M Laan, DP Strachan, P Sever, DC Shields, A Stanton, P Vollenweider, A Teumer, H Völzke, R Rettig, C Newton-Cheh, P Arora, F Zhang, N Soranzo, TD Spector, G Lucas, S Kathiresan, DS Siscovick, J Luan, RJ Loos, NJ Wareham, BW Penninx, IM Nolte, M McBride, WH Miller, SA Nicklin, AH Baker, D Graham, RA McDonald, JP Pell, N Sattar, P Welsh, P Munroe, MJ Caulfield, A Zanchetti, AF Dominiczak

TITLE:

Genome-wide association study of blood pressure extremes identifies variant near UMOD associated with hypertension.

JOURNAL:

PLoS genetics Oct 2010, Vol 6, pp. e1001177

ABSTRACT:

Hypertension is a heritable and major contributor to the global burden of disease. The sum of rare and common genetic variants robustly identified so far explain only 1%-2% of the population variation in BP and hypertension. This suggests the existence of more undiscovered common variants. We conducted a genome-wide association study in 1,621 hypertensive cases and 1,699 controls and follow-up validation analyses in 19,845 cases and 16,541 controls using an extreme case-control design. We identified a locus on chromosome 16 in the 5' region of Uromodulin (UMOD; rs13333226, combined P value of 3.6 × 10⁻¹¹). The minor G allele is associated with a lower risk of hypertension (OR [95%CI]: 0.87 [0.84-0.91]), reduced urinary uromodulin excretion, better renal function; and each copy of the G allele is associated with a 7.7% reduction in risk of CVD events after adjusting for age, sex, BMI, and smoking status (H.R. = 0.923, 95% CI 0.860-0.991; p = 0.027). In a subset of 13,446 individuals with estimated glomerular filtration rate (eGFR) measurements, we show that rs13333226 is independently associated with hypertension (unadjusted for eGFR: 0.89 [0.83-0.96], p = 0.004; after eGFR adjustment: 0.89 [0.83-0.96], p = 0.003). In clinical functional studies, we also consistently show the minor G allele is associated with lower urinary uromodulin excretion. The exclusive expression of uromodulin in the thick portion of the ascending limb of Henle suggests a putative role of this variant in hypertension through an effect on sodium homeostasis. The newly discovered UMOD locus for hypertension has the potential to give new insights into the role of uromodulin in BP regulation and to identify novel drugable targets for reducing cardiovascular risk. PUBMED: 21082022
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