Valvular & structural heart disease
Novel Association of the NOTCH Pathway Regulator MIB1 Gene With the Development of Bicuspid Aortic Valve
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
Methodological detailsmulticentre, familial discovery cohort with replication cohorts, in vivo mouse models, Data analysed October 2019 to October 2022
- Multicentre
- Familial discovery cohort with replication cohorts
- In vivo mouse models
- Data analysed October 2019 to October 2022
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.
Summarised from the published abstract; every number is checked against it