6533b836fe1ef96bd12a0b74

RESEARCH PRODUCT

Transcriptome-Wide Analysis Identifies Novel Associations With Blood Pressure.

Christian P. MüllerThomas MeitingerFrancisco OjedaHolger ProkischMarcus DörrXiuqing GuoLicia IacovielloPhilipp S. WildKatharina SchrammJohannes T NeumannStefan BlankenbergArne SchillertKuulasmaa KariUwe VölkerMaren Carstensen-kirbergGeorg HomuthWalter PalmasClaudia SchurmannAlexander TeumerSimone WahlAdelheid KratzerRenate B. SchnabelJerome I. RotterMahir KarakasTanja ZellerStephan B. FelixAndreas ZieglerSimona CostanzoDavid-alexandre TrégouëtYongmei LiuJingzhong DingKarl J. LacknerChristian GiegerPetra WolfUlf LandmesserAnnika JagodzinskiTim KacprowskiMichael RodenSoonil KwonDavid M. HerringtonChristian Herder

subject

0301 basic medicineMaleCandidate geneGene ExpressionGenome-wide association studyBlood Pressure030204 cardiovascular system & hematologyCardiorespiratory Medicine and HaematologyCardiovascularLMNATranscriptome0302 clinical medicineRisk FactorsCEBPAGene expression2.1 Biological and endogenous factorsAetiologyGeneticsMyelin and Lymphocyte-Associated Proteolipid ProteinsBlood Pressure ; Gene Expression ; Genome-wide Association Study ; Hypertension ; Transcriptomeblood pressureGenomicsSingle NucleotideLIM Domain Proteinsblood pressure; gene expression; genome-wide association study; hypertension; transcriptomeStrokeHeart DiseaseHypertensionPublic Health and Health ServicesBiomarker (medicine)FemaleEssential HypertensionPoly(ADP-ribose) PolymerasesBiotechnologyAdulthypertensionClinical SciencesNucleoside Transport ProteinsBiologyPolymorphism Single NucleotideArticle03 medical and health sciencesClinical ResearchInternal MedicineGeneticsHumansPolymorphismgenome-wide association studyGene Expression ProfilingHuman GenomeBlood Pressure DeterminationGene expression profiling030104 developmental biologyGood Health and Well BeingCardiovascular System & Hematologygene expressionCCAAT-Enhancer-Binding ProteinsCarrier ProteinstranscriptomeTranscription Factors

description

Hypertension represents a major cardiovascular risk factor. The pathophysiology of increased blood pressure (BP) is not yet completely understood. Transcriptome profiling offers possibilities to uncover genetics effects on BP. Based on 2 populations including 2549 individuals, a meta-analyses of monocytic transcriptome-wide profiles were performed to identify transcripts associated with BP. Replication was performed in 2 independent studies of whole-blood transcriptome data including 1990 individuals. For identified candidate genes, a direct link between long-term changes in BP and gene expression over time and by treatment with BP-lowering therapy was assessed. The predictive value of protein levels encoded by candidate genes for subsequent cardiovascular disease was investigated. Eight transcripts ( CRIP1 , MYADM , TIPARP , TSC22D3 , CEBPA , F12, LMNA , and TPPP3 ) were identified jointly accounting for up to 13% (95% confidence interval, 8.7–16.2) of BP variability. Changes in CRIP1 , MYADM , TIPARP , LMNA , TSC22D3 , CEBPA , and TPPP3 expression associated with BP changes—among these, CRIP1 gene expression was additionally correlated to measures of cardiac hypertrophy. Assessment of circulating CRIP1 (cystein-rich protein 1) levels as biomarkers showed a strong association with increased risk for incident stroke (hazard ratio, 1.06; 95% confidence interval, 1.03–1.09; P =5.0×10 –5 ). Our comprehensive analysis of global gene expression highlights 8 novel transcripts significantly associated with BP, providing a link between gene expression and BP. Translational approaches further established evidence for the potential use of CRIP1 as emerging disease-related biomarker.

yearjournalcountryeditionlanguage
2017-10-01
https://escholarship.org/uc/item/8bf9j0jr