Prevention & lipidsMeta-analysis
PCSK9 genetic variants and risk of vascular and non-vascular diseases in Chinese and UK populations
- Mendelian randomisation study (phenome-wide genetic association analysis)
- prospective biobank
- genetic score of 3 PCSK9 variants
- replication with UK Biobank meta-analysis
Authors' conclusion
The LDL-C-lowering PCSK9 genetic variants are associated with lower risk of subclinical and clinical atherosclerotic vascular disease but higher risks of respiratory diseases.
Study context
- Population
- Participants of the China Kadoorie Biobank (replication with UK Biobank)over 100,000 (lay summary)
- Comparison
- PCSK9 genetic score
Pooled result
As reported in the abstract
PCSK9-GS associations, per 1 SD lower LDL-C
PCSK9-GSOdds ratio (95% CI)P value
carotid plaque, n = 8340 cases
0.61(0.45–0.83)
P = 0.0015major occlusive vascular events, n = 15 752
0.80(0.67–0.95)
P = 0.011ischaemic stroke, n = 11 467
0.80(0.66–0.98)
P = 0.029Per 1 SD lower LDL-C, as printed
Further pooled results
Polygenic low-density lipoprotein cholesterol (LDL-C) score vs chronic obstructive pulmonary disease (COPD) hospitalization, COPD exacerbation, upper respiratory tract infection (URTI)
- No association
Safety
Respiratory diseases (PCSK9 genetic score (PCSK9-GS) / PCSK9 variant)
| Comparison | Estimate | P value | |
|---|---|---|---|
| PCSK9-GS · COPD hospitalization, n = 6836 | OR 1.38 (95% CI 1.08–1.76) | P = 0.0089 | |
| PCSK9-GS · fatal exacerbations in pre-existing COPD, n = 730 | OR 3.61 (95% CI 1.71–7.60) | P = 7.3 × 10-4 | |
| PCSK9 variant · acute URTI, meta-analysis with UK Biobank | pooled OR 1.87 (CI 1.38–2.54) | P = 5.4 × 10-5 | |
| PCSK9 variant · self-reported asthma | pooled OR 1.17 (CI 1.04–1.30) | P = 0.0071 | |
| 0.10.31310Ratio (log scale) |
Original publication
PCSK9 genetic variants and risk of vascular and non-vascular diseases in Chinese and UK populations. Eur J Prev Cardiol. Published 10 January 2024. doi:10.1093/eurjpc/zwae009
Summarised from the published abstract; every number is checked against it