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Genetic correlations and causal inferences in ischemic stroke.

Huan Cai1, Biyang Cai2, Zhonghua Liu1

  • 1Department of Rehabilitation, Zhongshan City People's Hospital, Zhongshan, 528403, Guangdong, China.

Journal of Neurology
|March 16, 2020
PubMed
Summary

Genetic factors link ischemic stroke risk to cholesterol levels, particularly LDL.P and LDL.C, especially in large artery stroke. Further research is needed to confirm these findings.

Keywords:
Ischemic strokeLinkage disequilibrium score regressionMendelian randomizationRisk factorSingle nucleotide polymorphism

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Area of Science:

  • Genetics
  • Epidemiology
  • Cardiovascular Research

Background:

  • Observational studies show inconsistent links between ischemic stroke and various risk factors.
  • Confounding in observational studies may explain these inconsistencies.

Purpose of the Study:

  • To assess genetic correlations between ischemic stroke and diverse phenotypes.
  • To investigate causal relationships between ischemic stroke and various traits using genetic data.

Main Methods:

  • Utilized summary-level data for ischemic stroke from the MEGASTROKE consortium.
  • Employed linkage disequilibrium score regression for genetic correlation analysis.
  • Applied Mendelian randomization (MR) to infer causal relationships, with sensitivity analyses.

Main Results:

  • Identified genetic overlaps between ischemic stroke and physical activity, cardiometabolic factors, smoking, and lung function.
  • Found suggestive evidence that genetic predisposition to higher low-density lipoprotein particles (LDL.P) and cholesterol (LDL.C) increases ischemic stroke risk, especially large artery stroke.
  • Observed robust associations of genetically predicted LDL.P and LDL.C with coronary artery disease and myocardial infarction.

Conclusions:

  • Genetic overlaps suggest shared pathways between ischemic stroke and lifestyle/cardiometabolic factors.
  • Provided evidence for a potential causal role of LDL.P and LDL.C in ischemic stroke, particularly large artery stroke.
  • Highlighted the need for future research to validate these genetic findings.