Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci.
Chunyu LiuAldi T KrajaJennifer A SmithJennifer A BrodyNora FranceschiniJoshua C BisKenneth RiceAlanna C MorrisonYingchang LuStefan WeissXiuqing GuoWalter PalmasLisa W MartinYii-Der Ida ChenPraveen SurendranFotios DrenosJames P CookPaul L AuerAudrey Y ChuAyush GiriWei ZhaoJohanna JakobsdottirLi-An LinJeanette M StaffordNajaf AminHao MeiJie YaoArend Voormannull nullnull nullnull nullnull nullMartin G LarsonMegan L GroveAlbert Vernon SmithShih-Jen HwangHan-Yang ChenTianxiao HuanGulum KosovaNathan O StitzielSekar KathiresanNilesh SamaniHeribert SchunkertPanagiotis Deloukasnull nullMan LiChristian FuchsbergerCristian PattaroMathias Gorskinull nullCharles KooperbergGeorge J PapanicolaouJacques E RossouwJessica D FaulSharon L R KardiaClaude BouchardLeslie J RaffelAndré G UitterlindenOscar H FrancoRamachandran S VasanChristopher J O'DonnellKent D TaylorKiang LiuErwin P BottingerOmri GottesmanE Warwick DawFranco GiulianiniSanthi GaneshElias SalfatiTamara B HarrisLenore J LaunerMarcus DörrStephan B FelixRainer RettigHenry VölzkeEric KimWen-Jane LeeI-Te LeeWayne H-H SheuKrystal S TsosieDigna R Velez EdwardsYongmei LiuAdolfo CorreaDavid R WeirUwe VölkerPaul M RidkerEric BoerwinkleVilmundur GudnasonAlexander P ReinerCornelia M van DuijnIngrid B BoreckiTodd L EdwardsAravinda ChakravartiJerome I RotterBruce M PsatyRuth J F LoosMyriam FornageGeorg B EhretChristopher Newton-ChehDaniel LevyDaniel I ChasmanPublished in: Nature genetics (2016)
Meta-analyses of association results for blood pressure using exome-centric single-variant and gene-based tests identified 31 new loci in a discovery stage among 146,562 individuals, with follow-up and meta-analysis in 180,726 additional individuals (total n = 327,288). These blood pressure-associated loci are enriched for known variants for cardiometabolic traits. Associations were also observed for the aggregation of rare and low-frequency missense variants in three genes, NPR1, DBH, and PTPMT1. In addition, blood pressure associations at 39 previously reported loci were confirmed. The identified variants implicate biological pathways related to cardiometabolic traits, vascular function, and development. Several new variants are inferred to have roles in transcription or as hubs in protein-protein interaction networks. Genetic risk scores constructed from the identified variants were strongly associated with coronary disease and myocardial infarction. This large collection of blood pressure-associated loci suggests new therapeutic strategies for hypertension, emphasizing a link with cardiometabolic risk.
Keyphrases
- genome wide
- copy number
- blood pressure
- dna methylation
- hypertensive patients
- systematic review
- meta analyses
- heart rate
- protein protein
- small molecule
- coronary artery disease
- heart failure
- gene expression
- coronary artery
- randomized controlled trial
- genome wide association study
- left ventricular
- high throughput
- aortic valve
- transcatheter aortic valve replacement
- genome wide association
- glycemic control