Positive genetic effect of hypertension family history on stroke: A cross Mendelian randomization study

J Stroke Cerebrovasc Dis. 2024 Oct;33(10):107901. doi: 10.1016/j.jstrokecerebrovasdis.2024.107901. Epub 2024 Aug 2.

Abstract

Background: Clinical observational study demonstrated that hypertension is an independent risk factor for stroke. Furthermore, both hypertension and stroke exhibit genetic predispositions. However, the genetic relationship between hypertension and stroke in first-degree relatives remains unclear.

Method: The Genetic effects were validated using an across-Mendelian randomization (MR) approach. The Genome-Wide Association Study summary data used in this study were obtained from a publicly available platform. The primary MR effect employed was inverse-variance weighted (IVW), and the other analysis methods included MR-Egger, weighted median, simple mode, and weighted mode. Prior to MR analysis, tests for MR_PRESSO, pleiotropy, and heterogeneity were conducted.

Result: The presence of family history of hypertension significantly contributed to the genetic predisposition to various types of stroke, including ischemic stroke, subarachnoid hemorrhage, lacunar stroke, cardioembolic ischemic stroke, small vessel ischemic stroke, and large artery atherosclerosis-related ischemic stroke.

Conclusion: Briefly, hypertension in first-degree relatives has a genetic impact on the risk of stroke development. Shared genetic factors may exist between hypertension and stroke.

Keywords: Causality effect; Hypertension; Mendelian randomization; Stroke.

MeSH terms

  • Blood Pressure / genetics
  • Databases, Genetic
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study*
  • Heredity*
  • Humans
  • Hypertension* / diagnosis
  • Hypertension* / epidemiology
  • Hypertension* / genetics
  • Hypertension* / physiopathology
  • Mendelian Randomization Analysis*
  • Pedigree
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Risk Assessment
  • Risk Factors
  • Stroke* / diagnosis
  • Stroke* / epidemiology
  • Stroke* / genetics