Genome-wide association study identifies eight loci associated with blood pressure

Abstract

Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5m genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N≤71,225 European ancestry, N=12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N=29,136). We identified association between systolic or diastolic blood pressure and common variants in 8 regions near the CYP17A1 (P=7×10−24), CYP1A2 (P=1×10−23), FGF5 (P=1×10−21), SH2B3 (P=3×10−18), MTHFR (P=2×10−13), c10orf107 (P=1×10−9), ZNF652 (P=5×10−9) and PLCD3 (P=1×10−8) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.

Genetic influence on blood pressure measured in the office, under laboratory stress and during real life

“…47 Another piece of evidence is from the recent genome wide association study on BP by the GLOBALBPGEN consortium. 48 Out of the six replication cohorts, the one with BP measured by Dinamap showed consistently lower standard errors (and P -values) for the effects of eight newly identified BP loci, suggesting that BP measured by Dinamap is accurate and reliable. Fourth, diary records during ABP monitoring were not collected, whereas recent efforts to characterize laboratory-to-life generalizability have been using the diary records to identify periods of psychosocial demand.…”

Codon 72 polymorphism (rs1042522) of TP53 is associated with changes in diastolic blood pressure over time

“…[15][16][17][18][19][20][21][22][23] As these studies have a cross-sectional design, it is not possible to examine the effect of a SNP on development of a trait. We suggest that rs1042522 has a role in the development of DBP and waist circumference during ageing and therefore, a SNP effect alone will be less informative compared with a SNP*time interaction in this case.…”

The impact of genome‐wide association studies on the pathophysiology and therapy of cardiovascular disease

“…Bearing in mind that the risk allele at the SH2B3 locus is also associated with increased platelet count (Soranzo et al , 2009), altered Sh2b3/Lnk function—as present in the mouse—seems to be a suitable model to analyse the functional impact of the variant in CAD. Besides the platelet phenotypes (Soranzo et al , 2009; Takizawa et al , 2010) and the also known association with blood pressure (Levy et al , 2009; Newton‐Cheh et al , 2009), SH2B3 seems to mainly influence inflammatory processes. From a genetic point of view, this is already noticeable from the associations of the locus with different inflammatory diseases, for example coeliac disease (Hunt et al , 2008), type 1 diabetes (Barrett et al , 2009; Concannon et al , 2009) and high eosinophil numbers (Gudbjartsson et al , 2009).…”

“…A score build on the cumulative effects of these loci displays a strong association with CAD (Levy et al , 2009; Newton‐Cheh et al , 2009; International Consortium for Blood Pressure Genome‐Wide Association Studies et al , 2011). Among the loci identified, there are several which are also genome‐wide significantly associated with CAD (Table 2, Fig 3B).…”