Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk.
Helen R WarrenEvangelos EvangelouClaudia P CabreraHe GaoMeixia RenBorbala MifsudIoanna NtallaPraveen SurendranChunyu LiuJames P CookAldi T KrajaFotios DrenosMarie LohNiek VerweijJonathan MartenIbrahim KaramanMarcelo P Segura LepePaul F O'ReillyJoanne KnightHarold SniederNorihiro KatoJiang HeE Shyong TaiM Abdullah SaidDavid J PorteousMaris AlverNeil PoulterMartin FarrallRon T GansevoortSandosh PadmanabhanReedik MägiAlice V StantonJohn ConnellStephan J L BakkerAndres MetspaluDenis C ShieldsSimon A M ThomMorris BrownPeter SeverTõnu EskoCaroline HaywardPim van der HarstDanish SaleheenRajiv ChowdhuryJohn C ChambersDaniel I ChasmanAravinda ChakravartiChristopher Newton-ChehCecilia M LindgrenDaniel LevyJaspal S KoonerBernard D KeavneyMaciej TomaszewskiNilesh J SamaniJoanna M M HowsonMartin D TobinPatricia B MunroeGeorg B EhretLouise V Wainnull nullnull nullnull nullnull nullnull nullnull nullnull nullnull nullnull nullnull nullnull nullPublished in: Nature genetics (2017)
Elevated blood pressure is the leading heritable risk factor for cardiovascular disease worldwide. We report genetic association of blood pressure (systolic, diastolic, pulse pressure) among UK Biobank participants of European ancestry with independent replication in other cohorts, and robust validation of 107 independent loci. We also identify new independent variants at 11 previously reported blood pressure loci. In combination with results from a range of in silico functional analyses and wet bench experiments, our findings highlight new biological pathways for blood pressure regulation enriched for genes expressed in vascular tissues and identify potential therapeutic targets for hypertension. Results from genetic risk score models raise the possibility of a precision medicine approach through early lifestyle intervention to offset the impact of blood pressure-raising genetic variants on future cardiovascular disease risk.
Keyphrases
- blood pressure
- genome wide
- cardiovascular disease
- hypertensive patients
- genome wide association
- heart rate
- copy number
- type diabetes
- genome wide association study
- dna methylation
- metabolic syndrome
- blood glucose
- physical activity
- gene expression
- adipose tissue
- left ventricular
- climate change
- weight loss
- atrial fibrillation