PuSH - Publikationsserver des Helmholtz Zentrums München: Discovery of genetic variation on chromosome 5q22 associated with mortality in heart failure.

Informationen

Hinweise zu Qualitätskriterien von Zeitschriften

Open-Access-Richtlinie der Helmholtz-Gemeinschaft 2016

CC Licencences

Metriken für Publikationen

Navigation

Startseite

English

EVA: Veröffentlichen

Neuer EVA Antrag

Recherche

Erweiterte Suche

Durchblättern nach ...

... HMGU-Autoren/Konsortien

... Organisationsstruktur

... Zeitschriften

... Publikationstypen

... Forschungsdaten

... Arbeitsgruppen

... Erscheinungsjahr

Publikationen im Überblick

Statistik

HGF Fortschrittsbericht

OA Publikationen

Eintragen

Neue Publikation eintragen

Neue Publikation holen aus...

...EVA

Fehlende Publikation melden

Highlights

Suche

Hilfe & Kontakt

Ansprechpartner

Hilfe

Datenschutz

Helmholtz Open Science

Bibliometrische Indikatoren

SHERPA/RoMEO

DOAJ

Export:

Text

Endnote (RIS) BIB

BibTeX

Smith, J.G.* ; Felix, J.F.* ; Morrison, A.C.* ; Kalogeropoulos, A.* ; Trompet, S.* ; Wilk, J.B.* ; Gidlöf, O.* ; Wang, X.* ; Morley, M.* ; Mendelson, M.* ; Joehanes, R.* ; Ligthart, S.* ; Shan, X.* ; Bis, J.C.* ; Wang, Y.A.* ; Sjögren, M.* ; Ngwa, J.S.* ; Brandimarto, J.* ; Stott, D.J.* ; Aguilar, D.* ; Rice, K.M.* ; Sesso, H.D.* ; Demissie, S.* ; Buckley, B.M.* ; Taylor, K.D.* ; Ford, I.* ; Yao, C.* ; Liu, C.* ; CHARGE-SCD Consortium (Butler, J.) ; EchoGen Consortium (Vasan, R.S. ; Cappola, T.P.) ; QT-IGC Consortium (Smith, N.L. ; Gieger, C. ; Perz, S. ; Peters, A. ; Pfeufer, A. ; Waldenberger, M. ; Crotti, L.) ; CHARGE-QRS Consortium (Klopp, N. ; Müller-Nurasyid, M. ; Perz, S. ; Wichmann, H.-E. ; Meitinger, T.) ; Sotoodehnia, N.* ; van der Harst, P.* ; Stricker, B.H.* ; Kritchevsky, S.B.* ; Liu, Y.* ; Gaziano, J.M.* ; Hofman, A.* ; Moravec, C.S.* ; Uitterlinden, A.G.* ; Kellis, M.* ; van Meurs, J.B.* ; Margulies, K.B.* ; Dehghan, A.* ; Levy, D.* ; Olde, B.* ; Psaty, B.M.* ; Cupples, L.A.* ; Jukema, J.W.* ; Djousse, L.* ; Franco, O.H.* ; Boerwinkle, E.* ; Boyer, L.A.* ; Newton-Cheh, C.*

Discovery of genetic variation on chromosome 5q22 associated with mortality in heart failure.

PLoS Genet. 12:e1006034 (2016)

Verlagsversion

DOI

PMC

	Open Access Gold

Abstract
Metriken
Zusatzinfos

Failure of the human heart to maintain sufficient output of blood for the demands of the body, heart failure, is a common condition with high mortality even with modern therapeutic alternatives. To identify molecular determinants of mortality in patients with new-onset heart failure, we performed a meta-analysis of genome-wide association studies and follow-up genotyping in independent populations. We identified and replicated an association for a genetic variant on chromosome 5q22 with 36% increased risk of death in subjects with heart failure (rs9885413, P = 2.7x10-9). We provide evidence from reporter gene assays, computational predictions and epigenomic marks that this polymorphism increases activity of an enhancer region active in multiple human tissues. The polymorphism was further reproducibly associated with a DNA methylation signature in whole blood (P = 4.5x10-40) that also associated with allergic sensitization and expression in blood of the cytokine TSLP (P = 1.1x10-4). Knockdown of the transcription factor predicted to bind the enhancer region (NHLH1) in a human cell line (HEK293) expressing NHLH1 resulted in lower TSLP expression. In addition, we observed evidence of recent positive selection acting on the risk allele in populations of African descent. Our findings provide novel genetic leads to factors that influence mortality in patients with heart failure.

Impact Factor

Scopus SNIP

Web of Science
Times Cited

Scopus
Cited By

Altmetric

6.661

1.522