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Corrected QT Interval-Polygenic Risk Score and Its Contribution to Type 1, Type 2, and Type 3 Long-QT Syndrome in Probands and Genotype-Positive Family Members.
Turkowski, Kari L; Dotzler, Steven M; Tester, David J; Giudicessi, John R; Bos, J Martijn; Speziale, Ashley D; Vollenweider, Jason M; Ackerman, Michael J.
Afiliación
  • Turkowski KL; Mayo Clinic Graduate School of Biomedical Sciences (K.L.T., S.M.D.), Mayo Clinic, Rochester, MN, USA.
  • Dotzler SM; Windland Smith Rice Sudden Death Genomics Laboratory, Department of Molecular Pharmacology & Experimental Therapeutics (K.L.T., S.M.D., D.J.T., J.M.B., M.J.A.), Mayo Clinic, Rochester, MN, USA.
  • Tester DJ; Mayo Clinic Graduate School of Biomedical Sciences (K.L.T., S.M.D.), Mayo Clinic, Rochester, MN, USA.
  • Giudicessi JR; Windland Smith Rice Sudden Death Genomics Laboratory, Department of Molecular Pharmacology & Experimental Therapeutics (K.L.T., S.M.D., D.J.T., J.M.B., M.J.A.), Mayo Clinic, Rochester, MN, USA.
  • Bos JM; Windland Smith Rice Sudden Death Genomics Laboratory, Department of Molecular Pharmacology & Experimental Therapeutics (K.L.T., S.M.D., D.J.T., J.M.B., M.J.A.), Mayo Clinic, Rochester, MN, USA.
  • Speziale AD; Clinician-Investigator Training Program, Department of Cardiovascular Medicine (J.R.G.), Mayo Clinic, Rochester, MN, USA.
  • Vollenweider JM; Windland Smith Rice Sudden Death Genomics Laboratory, Department of Molecular Pharmacology & Experimental Therapeutics (K.L.T., S.M.D., D.J.T., J.M.B., M.J.A.), Mayo Clinic, Rochester, MN, USA.
  • Ackerman MJ; Division of Pediatric Cardiology, Department of Pediatric and Adolescent Medicine (J.M.B., M.J.A.), Mayo Clinic, Rochester, MN, USA.
Circ Genom Precis Med ; 13(4): e002922, 2020 08.
Article en En | MEDLINE | ID: mdl-32469608
BACKGROUND: Long-QT syndrome (LQTS) is characterized by a prolonged heart rate-corrected QT interval (QTc). Genome-wide association studies identified common genetic variants that collectively explain ≈8% to 10% of QTc variation in the general population. METHODS: Overall, 423 patients with LQT1, LQT2, or LQT3 were genotyped for 61 QTc-associated genetic variants used in a prototype QTc-polygenic risk score (QTc-PRS). A weighted QTc-PRS (range, 0-154.8 ms) was calculated for each patient, and the FHS (Framingham Heart Study) population-based reference cohort (n=853). RESULTS: The average QTc-PRS in LQTS was 88.0±7.2 and explained only ≈2.0% of the QTc variability. The QTc-PRS in LQTS probands (n=137; 89.3±6.8) was significantly greater than both FHS controls (87.2±7.4, difference-in-means±SE: 2.1±0.7, P<0.002) and LQTS genotype-positive family members (87.5±7.4, difference-in-mean, 1.8±.7, P<0.009). There was no difference in QTc-PRS between symptomatic (n=156, 88.6±7.3) and asymptomatic patients (n=267; 87.7±7.2, difference-in-mean, 0.9±0.7, P=0.15). LQTS patients with a QTc≥480 ms (n=120) had a significantly higher QTc-PRS (89.3±6.7) than patients with a QTc<480 ms (n=303, 87.6±7.4, difference-in-mean, 1.7±0.8, P<0.05). There was no difference in QTc-PRS or QTc between genotypes. CONCLUSIONS: The QTc-PRS explained <2% of the QTc variability in our LQT1, LQT2, and LQT3 cohort, contributing 5× less to their QTc value than in the general population. This prototype QTc-PRS does not distinguish/predict the clinical outcomes of individuals with LQTS.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Síndrome de QT Prolongado / Polimorfismo de Nucleótido Simple Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Idioma: En Revista: Circ Genom Precis Med Año: 2020 Tipo del documento: Article

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Síndrome de QT Prolongado / Polimorfismo de Nucleótido Simple Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Idioma: En Revista: Circ Genom Precis Med Año: 2020 Tipo del documento: Article