Genome-wide association study identifies eight loci associated with blood pressure.
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 2.5 million 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 eight 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.
Newton-Cheh
Christopher
C
Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA. cnewtoncheh@chgr.mgh.harvard.edu
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D048868:Adaptor Proteins, Signal Transducing; D001794:Blood Pressure / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000235:genetics* / Q000503:physiopathology; D002874:Chromosome Mapping; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D003971:Diastole / Q000235:genetics; D005060:Europe; D051521:Fibroblast Growth Factor 5 / Q000235:genetics; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D007194:India; D047908:Intracellular Signaling Peptides and Proteins; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D016366:Open Reading Frames / Q000235:genetics; D054803:Phospholipase C delta / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics; D013599:Systole / Q000235:genetics; D044465:White People / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C496449:FGF5 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; C490778:SH2B3 protein, human; C525993:ZNF652 protein, human; D051521:Fibroblast Growth Factor 5; C504573:CYP1A2 protein, human; D019388:Cytochrome P-450 CYP1A2; C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase; D042965:Methylenetetrahydrofolate Reductase (NADPH2); C518028:PLCD3 protein, human; D054803:Phospholipase C delta