Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Rare truncating variants in the sarcomeric protein titin associate with familial and early-onset atrial fibrillation

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Capsid-like particles decorated with the SARS-CoV-2 receptor-binding domain elicit strong virus neutralization activity

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Common variants in Alzheimer's disease and risk stratification by polygenic risk scores

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Reply to “Quality control requirements for the correct annotation of lipidomics data”

    Publikation: Bidrag til tidsskriftLetterForskningpeer review

  4. Ultraviolet radiation drives mutations in a subset of mucosal melanomas

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

A family history of atrial fibrillation constitutes a substantial risk of developing the disease, however, the pathogenesis of this complex disease is poorly understood. We perform whole-exome sequencing on 24 families with at least three family members diagnosed with atrial fibrillation (AF) and find that titin-truncating variants (TTNtv) are significantly enriched in these patients (P = 1.76 × 10−6). This finding is replicated in an independent cohort of early-onset lone AF patients (n = 399; odds ratio = 36.8; P = 4.13 × 10−6). A CRISPR/Cas9 modified zebrafish carrying a truncating variant of titin is used to investigate TTNtv effect in atrial development. We observe compromised assembly of the sarcomere in both atria and ventricle, longer PR interval, and heterozygous adult zebrafish have a higher degree of fibrosis in the atria, indicating that TTNtv are important risk factors for AF. This aligns with the early onset of the disease and adds an important dimension to the understanding of the molecular predisposition for AF.

OriginalsprogEngelsk
Artikelnummer4316
TidsskriftNature Communications
Vol/bind9
Udgave nummer1
ISSN2041-1723
DOI
StatusUdgivet - 1 dec. 2018

ID: 55584171