Genetics
Mendelian randomisation using 290,497 UK Biobank participants finds no causal link between Lp(a) and arterial stiffness (Eur J Clin Invest 2024)
Original title: Association of Lipoprotein(a) with arterial stiffness: A Mendelian randomization study
This two-sample Mendelian randomisation study tested whether Lp(a) causally influences pulse wave velocity (PWV), the gold-standard marker of arterial stiffness. Genetic variants associated with Lp(a) came from a UK Biobank GWAS (n = 290,497), while genetic associations with two PWV measures, brachial-ankle (baPWV) and carotid-femoral (cfPWV), came from a separate European GWAS (n = 7,000). Using 170 single nucleotide polymorphisms as instrumental variables and inverse-variance-weighted analysis, the authors found no evidence of a causal association between Lp(a) and either baPWV (beta -0.0005, p = 0.8) or cfPWV (beta -0.006, p = 0.16), results that were consistent across weighted median, mode-based, MR-Egger, and MR-PRESSO sensitivity analyses. Despite Lp(a)'s established causal role in atherosclerotic cardiovascular disease, this study finds no genetic evidence that Lp(a) causally affects arterial stiffness as measured by PWV.
Original abstract
Background: In this study we used Mendelian randomization (MR) to investigate the potential causal association of lipoprotein (a) [Lp(a)] levels with pulse wave velocity (PWV).
Methods: Genetic variants associated with Lp(a) were retrieved from the UK Biobank GWAS (N = 290,497). A non- overlapping GWAS based on a European cohort (N = 7,000) was used to obtain genetic associations with PWV (outcome) and utilized two different measures for the same trait, brachial-ankle (baPWV) and carotid-femoral (cfPWV) PWV. We applied a two-sample MR using the inverse variance weighting method (IVW) and a series of sensitivity analyses for 170 SNPs that were selected as instrumental variables (IVs).
Results: Our analyses do not support a causal association between Lp(a) and PWV for neither measurement [βiwv(baPWV) = -.0005, p = .8 and βiwv(cfPWV) = -.006, p = .16]. The above findings were consistent across sensitivity analyses including weighted median, mode-based estimation, MR-Egger regression and MR-PRESSO.
Conclusion: We did not find evidence indicating that Lp(a) is causally associated with PWV, the gold standard marker of arterial stiffness.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.