Trans-ethnic association study of blood pressure determinants in over 750,000 individuals.
Ayush GiriJacklyn N HellwegeJacob M KeatonJihwan ParkChengxiang QiuHelen R WarrenEric S TorstensonCsaba P KovesdyYan V SunOtis D WilsonCassianne Robinson-CohenChristianne L RoumieCecilia P ChungKelly A BirdwellScott M DamrauerScott L DuvallDerek KlarinKelly ChoYu WangEvangelos EvangelouClaudia P CabreraLouise V WainRojesh ShresthaBrian S MautzElvis A AkwoMuralidharan SargurupremrajStéphanie DebetteMichael BoehnkeLaura J ScottJian'an LuanJing-Hua ZhaoSara M WillemsSébastien ThériaultNabi ShahChristopher OldmeadowPeter AlmgrenRuifang Li-GaoNiek VerweijThibaud S BoutinMassimo ManginoIoanna NtallaElena Valeryevna FeofanovaPraveen SurendranJames P CookSavita KarthikeyanNajim LahrouchiChunyu LiuNuno SepúlvedaTom G RichardsonAldi KrajaPhillippe AmouyelMartin FarrallNeil R Poulternull nullnull nullnull nullMarkku LaaksoEleftheria ZegginiPeter SeverRobert A ScottClaudia LangenbergNicholas J WarehamDavid ConenColin Neil Alexander PalmerJohn Richard AttiaDaniel I ChasmanPaul M RidkerOlle MelanderDennis Owen Mook-KanamoriPim van der HarstFrancesco CuccaDavid SchlessingerCaroline HaywardTim D SpectorMarjo-Riitta JarvelinBranwen J HennigNicholas J TimpsonWei-Qi WeiJoshua C SmithYaomin XuMichael E MathenyEdward E SiewCecilia LindgrenKarl-Heinz HerzigGeorge DedoussisJoshua C DennyBruce M PsatyJoanna M M HowsonPatricia B MunroeChristopher Newton-ChehMark J CaulfieldPaul ElliottJ Michael GazianoJohn ConcatoPeter W F WilsonPhilip S TsaoDigna R Velez EdwardsKatalin Susztáknull nullChristopher J O'DonnellAdriana M HungTodd L EdwardsPublished in: Nature genetics (2018)
In this trans-ethnic multi-omic study, we reinterpret the genetic architecture of blood pressure to identify genes, tissues, phenomes and medication contexts of blood pressure homeostasis. We discovered 208 novel common blood pressure SNPs and 53 rare variants in genome-wide association studies of systolic, diastolic and pulse pressure in up to 776,078 participants from the Million Veteran Program (MVP) and collaborating studies, with analysis of the blood pressure clinical phenome in MVP. Our transcriptome-wide association study detected 4,043 blood pressure associations with genetically predicted gene expression of 840 genes in 45 tissues, and mouse renal single-cell RNA sequencing identified upregulated blood pressure genes in kidney tubule cells.
Keyphrases
- blood pressure
- hypertensive patients
- gene expression
- heart rate
- genome wide
- single cell
- dna methylation
- genome wide association
- emergency department
- heart failure
- healthcare
- rna seq
- copy number
- blood glucose
- metabolic syndrome
- oxidative stress
- skeletal muscle
- atrial fibrillation
- weight loss
- genome wide identification
- adverse drug