Rare GATA6 variants associated with risk of congenital heart disease phenotypes in 200,000 UK Biobank exomes
Open Access
- 7 September 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Journal of Human Genetics
- Vol. 67 (2), 123-125
- https://doi.org/10.1038/s10038-021-00976-0
Abstract
Congenital heart disease (CHD) has a complex and largely uncharacterised genetic etiology. Using 200,000 UK Biobank (UKB) exomes, we assess the burden of ultra-rare, potentially pathogenic variants in the largest case/control cohort of predominantly mild CHD to date. We find an association with GATA6, a member of the GATA family of transcription factors that play an important role during heart development and has been linked with several CHD phenotypes previously. Several identified GATA6 variants are previously unreported and their roles in conferring risk to CHD warrants further study. We demonstrate that despite limitations regarding detailed familial phenotype information in large-scale biobank projects, through careful consideration of case and control cohorts it is possible to derive important associations.Keywords
Funding Information
- British Heart Foundation (RG/15/12/31616)
This publication has 12 references indexed in Scilit:
- GATA6 mutations: Characterization of two novel patients and a comprehensive overview of the GATA6 genotypic and phenotypic spectrumAmerican Journal of Medical Genetics Part A, 2019
- Global birth prevalence of congenital heart defects 1970–2017: updated systematic review and meta-analysis of 260 studiesInternational Journal of Epidemiology, 2019
- GATA6 Regulates Aortic Valve Remodeling, and Its Haploinsufficiency Leads to Right-Left Type Bicuspid Aortic ValveJournal of the American College of Cardiology, 2018
- Comparison of Sociodemographic and Health-Related Characteristics of UK Biobank Participants With Those of the General PopulationAmerican Journal of Epidemiology, 2017
- Protein-altering and regulatory genetic variants near GATA4 implicated in bicuspid aortic valveNature Communications, 2017
- Contemporary natural history of bicuspid aortic valve disease: a systematic reviewHeart, 2017
- Novel GATA6 Mutations Associated with Congenital Ventricular Septal Defect or Tetralogy of FallotDNA and Cell Biology, 2012
- A novel GATA6 mutation associated with congenital ventricular septal defectInternational Journal of Molecular Medicine, 2012
- A novel GATA6 mutation in patients with tetralogy of Fallot or atrial septal defectJournal of Human Genetics, 2010
- GATA6 mutations cause human cardiac outflow tract defects by disrupting semaphorin-plexin signalingProceedings of the National Academy of Sciences of the United States of America, 2009