Valvular & structural heart disease
Dyslipidemia, inflammation, calcification, and adiposity in aortic stenosis: a genome-wide study
Authors' conclusion
Dyslipidemia, inflammation, calcification, and adiposity play important roles in the etiology of AS
Study context
- Population
- European ancestry participants; calcific aortic stenosis (AS)
- Participants
- 653,867 participants10 cohorts
- Outcome
- Genetic loci associated with AS (genome-wide significance P ≤ 5 × 10-8)
Methodological details10 cohorts, independent replication cohort, Mendelian randomization, phenome-wide association study, colocalization analyses (GTEx)
- 10 cohorts
- Independent replication cohort
- Mendelian randomization
- Phenome-wide association study
- Colocalization analyses (GTEx)
Pooled result
As reported in the abstract
Loci associated with AS
Loci associated with AS at P ≤ 5 × 10-8
17
Loci replicated in independent cohort (90 828 participants, 7111 cases), incl. CELSR2-SORT1, NLRP6, SMC2
15
Further pooled results
Genetic risk score of index variants and AS
| OR per SD (95% CI) | P value | ||
|---|---|---|---|
| Genetic risk scoreAdjusted for known risk factors | 1.31 (1.26–1.35) | P = 2.7 × 10-51 | |
| 0.512Odds ratio per SD (log scale) |
Genetic risk score and aortic valve calcium
| OR per SD (95% CI) | P value | ||
|---|---|---|---|
| Genetic risk scoreAdjusted for known risk factors | 1.22 (1.08–1.37) | P = 1.4 × 10-3 | |
| 0.512Odds ratio per SD (log scale) |
Mendelian randomization: causal risk factors for AS
| Estimate | P value | ||
|---|---|---|---|
| Apolipoprotein B | OR per g/L 3.85 (95% CI 2.90–5.12) | P = 2.1 × 10-20 | |
| Lipoprotein(a) | OR per natural logarithm 1.20 (95% CI 1.17–1.23) | P = 4.8 × 10-73 | |
| BMI | OR per kg/m² 1.07 (95% CI 1.05–1.9) | P = 1.9 × 10-12 | |
| 0.20.5125Ratio (log scale) |
Phenome-wide association study
- Multiple associations with CAD, apolipoprotein B and TG
Colocalization (GTEx)
- Role for differential expression of LPA, SORT1, ACTR2, NOTCH4, IL6R and FADS
Original publication
Dyslipidemia, inflammation, calcification, and adiposity in aortic stenosis: a genome-wide study. Eur Heart J. Published 11 April 2023. doi:10.
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