Genetically proxied low-density lipoprotein cholesterol lowering via PCSK9-inhibitor drug targets and risk of congenital malformations
Authors' conclusion
These data provide genetic evidence supporting current manufacturer advice to avoid the use of PCSK9 inhibitors during pregnancy.
Study context
- Population
- FinnGen cohort; 8 categories of congenital malformationsFinnGen cohort
- Participants
- 342,499 participants
- Comparison
- Genetically proxied LDL lowering via PCSK9 drug targets and risk of congenital malformations
- Outcome
- Congenital malformations (8 categories)
Methodological detailsLDL instruments from genome-wide association study (GWAS) on 1 320 016 individuals; PCSK9 pQTLs from GWAS on 10 186 individuals; liver eQTLs from genotype-tissue expression project
- LDL instruments from GWAS on 1 320 016 individuals; PCSK9 pQTLs from GWAS on 10 186 individuals; liver eQTLs from genotype-tissue expression project
Main finding
As reported in the abstract
Congenital malformations (FinnGen)
LDL-lowering through PCSK9Odds ratio (95% CI)P value
Malformations affecting multiple systems
2.70(1.30–5.63)
P = 0.018Skin
2.23(1.33–3.75)
P = 0.007VACTERL association
1.51(1.16–1.96)
P = 0.007Further findings
Obstructive defects of the renal pelvis and ureter
- Association found, but suggestive of horizontal pleiotropy
Lower PCSK9 pQTLs
- Associated with the same congenital malformations
Original publication
Genetically proxied low-density lipoprotein cholesterol lowering via PCSK9-inhibitor drug targets and risk of congenital malformations. Eur J Prev Cardiol. Published 31 January 2024. doi:10.
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