Causal relationship between lactate dehydrogenase and risk of developing ischemic stroke: A Mendelian randomized study

Abstract

Background and objective: Ischemic stroke (IS) is one of the major global health problems. It is not clear whether there is a causal relationship between lactate dehydrogenase (LDH) and the risk of IS attacks. The purpose of this study was to investigate whether LDH has a causal relationship with the development of IS.

Methods: The genome-wide association data of LDH and IS were obtained through a Mendelian randomization-based platform. Single nucleotide polymorphisms (SNP) that were significantly associated with LDH were identified and used as instrumental variables, and a two-sample Mendelian randomization study was used to examine the causal relationship between LDH and IS. The statistical methods included Inverse-variance weighted approach, MR-Egger regression, and weighted median estimator.

Results: We selected 15 SNPs of genome-wide significance from Genome-wide association study database with LDH as instrumental variables. A consistent causal association between LDH and IS was observed by different assessment methods. The results of the inverse-variance weighted method suggested an inverse association between LDH and higher genetic predictability of IS risk (OR, 0.997; 95%CI 0.995-0.999). The weighted median estimate showed consistent results with the MR-Egger method (weighted median estimate: OR, 0.995; 95%CI 0.992-0.999; MR-Egger method: OR, 0.996; 95%CI 0.992-0.999). The inverse-variance weighted method indicates a causal association between LDH and IS (β = -0.002563, SE = 0.00128, p = .0453). MR-Egger analysis (β = -0.004498, SE = 0.001877, p = .03) and the weighted median method suggested that LDH and IS also existed causal relationship (β = -0.004861, SE = 0.001801, p = .00695).

Conclusions: Our Mendelian randomization results suggest that LDH is inversely associated with the risk of developing IS, and are contrary to the results of previous observational studies.

Keywords: Mendelian randomization; ischemic stroke; lactate dehydrogenase.