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

Abstract

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

• ischemic stroke
• lactate dehydrogenase
• Mendelian randomization