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Published on: December 2, 2014
Association of Lipoprotein(a) with arterial stiffness: A Mendelian randomization study
Alexandros Simistiras1, Georgios Georgiopoulos1,2, Dimitrios Delialis1
1Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, Athens, Greece.
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.
