SwePub
Sök i LIBRIS databas

  Utökad sökning

WFRF:(Bamshad Michael)
 

Sökning: WFRF:(Bamshad Michael) > (2019) > Loss of function, m...

  • Helle, EmmiUniv Helsinki, Childrens Hosp, Pediat Res Ctr, Helsinki, Finland;Stanford Univ, Sch Med, Div Cardiovasc Med, Cardiovasc Med, Stanford, CA 94305 USA (författare)

Loss of function, missense, and intronic variants in NOTCH1 confer different risks for left ventricular outflow tract obstructive heart defects in two European cohorts

  • Artikel/kapitelEngelska2019

Förlag, utgivningsår, omfång ...

  • 2018-12-04
  • Wiley,2019
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:uu-381089
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-381089URI
  • https://doi.org/10.1002/gepi.22176DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Loss of function variants in NOTCH1 cause left ventricular outflow tract obstructive defects (LVOTO). However, the risk conferred by rare and noncoding variants in NOTCH1 for LVOTO remains largely uncharacterized. In a cohort of 49 families affected by hypoplastic left heart syndrome, a severe form of LVOTO, we discovered predicted loss of function NOTCH1 variants in 6% of individuals. Rare or low-frequency missense variants were found in 16% of families. To make a quantitative estimate of the genetic risk posed by variants in NOTCH1 for LVOTO, we studied associations of 400 coding and noncoding variants in NOTCH1 in 1,085 cases and 332,788 controls from the UK Biobank. Two rare intronic variants in strong linkage disequilibrium displayed significant association with risk for LVOTO amongst European-ancestry individuals. This result was replicated in an independent analysis of 210 cases and 68,762 controls of non-European and mixed ancestry. In conclusion, carrying rare predicted loss of function variants in NOTCH1 confer significant risk for LVOTO. In addition, the two intronic variants seem to be associated with an increased risk for these defects. Our approach demonstrates the utility of population-based data sets in quantifying the specific risk of individual variants for disease-related phenotypes.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Cordova-Palomera, AldoStanford Univ, Dept Pediat, Sch Med, Div Pediat Cardiol, Stanford, CA 94305 USA (författare)
  • Ojala, TiinaUniv Helsinki, Childrens Hosp, Pediat Res Ctr, Helsinki, Finland (författare)
  • Saha, PriyankaStanford Univ, Dept Pediat, Sch Med, Div Pediat Cardiol, Stanford, CA 94305 USA (författare)
  • Potiny, PraneethaStanford Univ, Dept Pediat, Sch Med, Div Pediat Cardiol, Stanford, CA 94305 USA (författare)
  • Gustafsson, StefanUppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylär epidemiologi(Swepub:uu)stegu732 (författare)
  • Ingelsson, Erik,1975-Uppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylär epidemiologi,Stanford Univ, Sch Med, Div Cardiovasc Med, Cardiovasc Med, Stanford, CA 94305 USA(Swepub:uu)ering425 (författare)
  • Bamshad, MichaelUniv Washington, Dept Pediat, Seattle, WA 98195 USA;Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA;Seattle Childrens Hosp, Div Genet Med, Seattle, WA USA (författare)
  • Nickerson, DeborahUniv Washington, Dept Genome Sci, Seattle, WA 98195 USA (författare)
  • Chong, Jessica X.Univ Washington, Dept Pediat, Seattle, WA 98195 USA (författare)
  • Ashley, EuanStanford Univ, Sch Med, Div Cardiovasc Med, Cardiovasc Med, Stanford, CA 94305 USA (författare)
  • Priest, James R.Stanford Univ, Sch Med, Div Cardiovasc Med, Cardiovasc Med, Stanford, CA 94305 USA;Stanford Univ, Dept Pediat, Sch Med, Div Pediat Cardiol, Stanford, CA 94305 USA (författare)
  • Univ Helsinki, Childrens Hosp, Pediat Res Ctr, Helsinki, Finland;Stanford Univ, Sch Med, Div Cardiovasc Med, Cardiovasc Med, Stanford, CA 94305 USAStanford Univ, Dept Pediat, Sch Med, Div Pediat Cardiol, Stanford, CA 94305 USA (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Genetic Epidemiology: Wiley43:2, s. 215-2260741-03951098-2272

Internetlänk

Hitta via bibliotek

Till lärosätets databas

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy