Valvular & structural heart diseaseCohort study
Novel Association of the NOTCH Pathway Regulator MIB1 Gene With the Development of Bicuspid Aortic Valve
- Genetic association study
- multicentre
- familial discovery cohort with replication cohorts
- in vivo mouse models
- Data analysed October 2019 to October 2022
Authors' conclusion
This genetic association study identified the MIB1 gene as associated with nsBAV.
Study context
- Population
- Patients with nonsyndromic bicuspid aortic valve (nsBAV)
- Participants
- 938 patients · 3 cohorts
- Exposure
- nsBAV cases vs population-based controls
- Discoveryn = 69
- Replication cohort 1n = 417
- Replication cohort 2n = 452
- Outcome
- Identification of a candidate gene for nsBAV by exome sequencing of familial cases and gene prioritization
Main finding
As reported in the abstract
Rare predicted-damaging MIB1 variants (discovery + replication 1 index cases)
P = 0.03
Observational data: associations, not effects.
Further findings
MIB1 risk haplotypes (replication cohort 2)
- Risk haplotypes significantly associated with nsBAV (permutation test, 1000 repeats)
- P = 0.02
Mouse models carrying Mib1 variants
- Two genetically modified models showed BAV on a NOTCH1-sensitized background
Original publication
Novel Association of the NOTCH Pathway Regulator MIB1 Gene With the Development of Bicuspid Aortic Valve. JAMA Cardiol. Published 1 August 2023. doi:10.1001/jamacardio.2023.1469
Summarised from the published abstract; every number is checked against it