Valvular & structural heart diseaseDiagnostic or prognostic study
Multisystem comorbidities and shared genetic pathways in calcific aortic stenosis: a phenome-wide and Mendelian randomisation analysis
- phenome-wide and Mendelian randomisation analysis
- observational and polygenic phenome-wide association studies
- disease-trajectory analyses
- two-sample Mendelian randomisation (MR)
- Polygenic risk score (PRS) analyses
Authors' conclusion
CAS is embedded within a broad multisystem comorbidity network, driven largely by genetic variation at LPA and elevated Lp(a). These findings highlight pleiotropic mechanisms linking valvular calcification with systemic disease and support LPA-targeted therapies as a promising avenue for reducing the multisystem burden of CAS.
Study context
- Population
- Participants from the UK Biobankparticipants from the UK Biobank
- Participants
- 467,484 participants
- Comparison
- Associations between calcific aortic stenosis (CAS) and 1571 phenotypes
Performance
As reported in the abstract
CAS associated with higher risks of cardiovascular and non-cardiovascular conditions, most prominently metabolic, endocrine, haematological and respiratory disorders
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Further findings
Temporal patterns of comorbidities
- Circulatory and metabolic diseases typically precede other comorbidities in CAS trajectories
MR causal effects of CAS
- Consistent with causal effects of CAS on multiple cardiovascular diseases, iron-deficiency anaemia, mental disorders and pleural effusion
PRS analyses excluding LPA variants or adjusting for plasma Lp(a)
- Most associations lost significance, indicating a shared LPA/Lp(a)-mediated genetic pathway
Original publication
Summarised from the published abstract; every number is checked against it