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Elizabeth G Holliday1, Matthew Traylor1, Rainer Malik1

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Stroke
|October 30, 2014
PubMed
Summary

Shared genetics may link kidney dysfunction and ischemic stroke (IS). This polygenic correlation appears specific to stroke subtypes, particularly large artery atherosclerotic stroke, warranting further investigation.

Keywords:
genetic epidemiologykidneystroke

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Area of Science:

  • Genetics
  • Nephrology
  • Neurology

Background:

  • Epidemiological studies reveal a strong link between kidney dysfunction and ischemic stroke (IS) risk.
  • The underlying biological mechanisms connecting these conditions remain unclear.

Purpose of the Study:

  • To investigate if shared heritability, due to a common polygenic basis, underlies the association between kidney dysfunction and IS.
  • To determine if this genetic association differs across IS subtypes.

Main Methods:

  • Polygenic models were developed using genome-wide association study meta-analysis data for estimated glomerular filtration rate (eGFRcrea and eGFRcys) and urinary albumin to creatinine ratio.
  • Single nucleotide polymorphisms were used to create profile scores in IS cases and controls from UK, Germany, and Australia.
  • Scores were analyzed for association with IS and its subtypes: large artery atherosclerosis, cardioembolism, and small vessel disease.

Main Results:

  • Polygenic scores for higher estimated glomerular filtration rate (eGFRcrea) were linked to reduced risk of large artery atherosclerosis.
  • Similar associations were found for polygenic scores reflecting higher urinary albumin to creatinine ratio, particularly with large artery atherosclerosis and small vessel disease.
  • The overall pattern of results suggested a non-random genetic correlation between renal dysfunction and IS subtypes.

Conclusions:

  • This study indicates a potential polygenic correlation between renal dysfunction and ischemic stroke.
  • Shared genetic factors may be particularly relevant for specific stroke subtypes, notably large artery atherosclerotic stroke.
  • Further research into the genetic interrelations between kidney disease and stroke is recommended.