Polygenic overlap between kidney function and large artery atherosclerotic stroke

Elizabeth G. Holliday, Matthew Traylor, Rainer Malik, Stephen Bevan, Jane Maguire, Simon A. Koblar, Jonathan Sturm, Graeme J. Hankey, Christopher Oldmeadow, Mark McEvoy, Cathie Sudlow, Peter M. Rothwell, Josef Coresh, Pavel Hamet, Johanne Tremblay, Stephen T. Turner, Mariza De Andrade, Madhumathi Rao, Reinhold Schmidt, Peter A. CrickAntonietta Robino, Carmen A. Peralta, J. Wouter Jukema, Paul Mitchell, Sylvia E. Rosas, Jie Jin Wang, Rodney J. Scott, Martin Dichgans, Braxton D. Mitchell, W. H Linda Kao, Caroline S. Fox, Christopher Levi, John Attia, Hugh S. Markus

Research output: Contribution to journalArticlepeer-review

Abstract

Background and Purpose - Epidemiological studies show strong associations between kidney dysfunction and risk of ischemic stroke (IS), the mechanisms of which are incompletely understood. We investigated whether these associations may reflect shared heritability because of a common polygenic basis and whether this differed for IS subtypes.

Methods - Polygenic models were derived using genome-wide association studies meta-analysis results for 3 kidney traits: estimated glomerular filtration rate using serum creatinine (eGFRcrea: n=73 998), eGFR using cystatin C (eGFRcys: n=22 937), and urinary albumin to creatinine ratio (n=31 580). For each, single nucleotide polymorphisms passing 10 P value thresholds were used to form profile scores in 4561 IS cases and 7094 controls from the United Kingdom, Germany, and Australia. Scores were tested for association with IS and its 3 aetiological subtypes: large artery atherosclerosis, cardioembolism, and small vessel disease.

Results - Polygenic scores correlating with higher eGFRcrea were associated with reduced risk of large artery atherosclerosis, with 5 scores reaching P

Conclusions - This study suggests possible polygenic correlation between renal dysfunction and IS. The shared genetic components may be specific to stroke subtypes, particularly large artery atherosclerotic stroke. Further study of the genetic relationships between these disorders seems merited.

Original languageEnglish
Pages (from-to)3508-3513
Number of pages6
JournalStroke
Volume45
Issue number12
DOIs
Publication statusPublished - Dec 11 2014

Keywords

  • Genetic epidemiology
  • Kidney
  • Stroke

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Advanced and Specialised Nursing
  • Medicine(all)

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