Polygenic overlap between kidney function and large artery atherosclerotic stroke

E.G. Holliday, M. Traylor, R. Malik, S. Bevan, J.M. Maguire, S.A. Koblar, J.W. Sturm, Graeme J. Hankey, C.J. Oldmeadow, M.A. Mcevoy, C.L.M. Sudlow, P.M.W. Rothwell, J. Coresh, P. Hamet, J. Tremblay, S.T. Turner, M. De Andrade, M. Rao, R. Schmidt, P.A. CrickA. Robino, C.A. Peralta, J.W.O. Jukema, P.G. Mitchell, S.E. Rosas, J. Wang, R.J. Scott, M. Dichgans, B.D. Mitchell, W.H.L. Kao, C.S. Fox, C.R. Levi, J.R. Attia, H.S. Markus

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    Abstract

    © 2014 American Heart Association, Inc. 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
    Original languageEnglish
    Pages (from-to)3508-3513
    JournalStroke
    Volume45
    Issue number12
    DOIs
    Publication statusPublished - Dec 2014

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