Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits.
Jacob M KeatonZoha KamaliTian XieAhmad VaezAriel WilliamsSlavina B GolevaAlireza AniEvangelos EvangelouJacklyn N HellwegeLoic YengoWilliam J YoungMatthew TraylorAyush GiriZhili ZhengJian ZengDaniel I ChasmanAndrew P MorrisMark J CaulfieldShih-Jen HwangJaspal S KoonerDavid ConenJohn Richard AttiaAlanna C MorrisonRuth J F LoosKati KristianssonReinhold SchmidtAndrew A HicksPeter Paul PramstallerChristopher P NelsonNilesh J SamaniLorenz RischUlf GyllenstenOlle MelanderHarriette RieseJames F WilsonHarry CampbellStephen S RichBruce M PsatyYingchang LuJerome I RotterXiuqing GuoKenneth M RicePeter VollenweiderJohan SundströmClaudia LangenbergMartin D TobinVilmantas GiedraitisJian'an LuanJaakko TuomilehtoZoltan KutalikSamuli RipattiVeikko V SalomaaGiorgia GirottoStella TrompetJ Wouter JukemaPim van der HarstPaul M RidkerFranco GiulianiniVeronique VitartAnuj GoelHugh C WatkinsSarah E HarrisIan J DearyPeter J van der MostAlbertine J OldehinkelBernard D KeavneyCaroline HaywardArchie I CampbellMichael BoehnkeLaura J ScottThibaud S BoutinChrysovalanto MamasoulaMarjo-Riitta JärvelinAnnette PetersChristian GiegerEdward L M LakattaFrancesco CuccaJennie HuiPaul KnektStefan EnrothMartin H de BorstOzren PolašekMaria Pina ConcasEulalia CatamoMassimiliano CoccaRuifang Li-GaoEdith HoferHelena SchmidtBeatrice SpedicatiMelanie WaldenbergerDavid P StrachanMaris LaanAlexander TeumerMarcus DörrVilmundur G GudnasonJames P CookDaniela RuggieroIvana KolčićEric BoerwinkleMichela TragliaTerho LehtimäkiOlli T RaitakariAndrew Danner JohnsonChristopher H Newton-ChehMorris J BrownAnna F DominiczakPeter J SeverNeil PoulterJohn C ChambersRoberto ElosuaDavid SiscovickTõnu EskoAndres MetspaluRona Juliette StrawbridgeMarkku LaaksoAnders HamstenJouke- Jan HottengaEco de GeusAndrew D MorrisColin Neil Alexander PalmerIlja Maria NolteYuri MilaneschiJonathan MartenAlan WrightEleftheria ZegginiJoanna M M HowsonChristopher J O'DonnellTimothy D SpectorMichael A NallsEleanor M SimonsickYongmei LiuCornelia M Van DuijnAdam S ButterworthJohn N DaneshCristina MenniNicholas J WarehamKay-Tee KhawYan V SunPeter W F WilsonKelly ChoPeter M VisscherJoshua C Dennynull nullnull nullnull nullnull nullDaniel LevyTodd L EdwardsPatricia B MunroeHarold SniederHelen R WarrenPublished in: Nature genetics (2024)
Hypertension affects more than one billion people worldwide. Here we identify 113 novel loci, reporting a total of 2,103 independent genetic signals (P < 5 × 10 -8 ) from the largest single-stage blood pressure (BP) genome-wide association study to date (n = 1,028,980 European individuals). These associations explain more than 60% of single nucleotide polymorphism-based BP heritability. Comparing top versus bottom deciles of polygenic risk scores (PRSs) reveals clinically meaningful differences in BP (16.9 mmHg systolic BP, 95% CI, 15.5-18.2 mmHg, P = 2.22 × 10 -126 ) and more than a sevenfold higher odds of hypertension risk (odds ratio, 7.33; 95% CI, 5.54-9.70; P = 4.13 × 10 -44 ) in an independent dataset. Adding PRS into hypertension-prediction models increased the area under the receiver operating characteristic curve (AUROC) from 0.791 (95% CI, 0.781-0.801) to 0.826 (95% CI, 0.817-0.836, ∆AUROC, 0.035, P = 1.98 × 10 -34 ). We compare the 2,103 loci results in non-European ancestries and show significant PRS associations in a large African-American sample. Secondary analyses implicate 500 genes previously unreported for BP. Our study highlights the role of increasingly large genomic studies for precision health research.