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Polygenic overlap between kidney function and large artery atherosclerotic stroke.
Holliday, Elizabeth G; Traylor, Matthew; Malik, Rainer; Bevan, Stephen; Maguire, Jane; Koblar, Simon A; Sturm, Jonathan; Hankey, Graeme J; Oldmeadow, Christopher; McEvoy, Mark; Sudlow, Cathie; Rothwell, Peter M; Coresh, Josef; Hamet, Pavel; Tremblay, Johanne; Turner, Stephen T; de Andrade, Mariza; Rao, Madhumathi; Schmidt, Reinhold; Crick, Peter A; Robino, Antonietta; Peralta, Carmen A; Jukema, J Wouter; Mitchell, Paul; Rosas, Sylvia E; Wang, Jie Jin; Scott, Rodney J; Dichgans, Martin; Mitchell, Braxton D; Kao, W H Linda; Fox, Caroline S; Levi, Christopher; Attia, John; Markus, Hugh S.
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  • Holliday EG; From the School of Medicine and Public Health (E.G.H., J.S., M.M., J.A.) and School of Nursing and Midwifery (J.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit (E.G.H., C.O., J.A.), Hunter Medical Research Institute (J.M., R.J.S., C.L.), Newcastle,
  • Traylor M; From the School of Medicine and Public Health (E.G.H., J.S., M.M., J.A.) and School of Nursing and Midwifery (J.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit (E.G.H., C.O., J.A.), Hunter Medical Research Institute (J.M., R.J.S., C.L.), Newcastle,
  • Malik R; From the School of Medicine and Public Health (E.G.H., J.S., M.M., J.A.) and School of Nursing and Midwifery (J.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit (E.G.H., C.O., J.A.), Hunter Medical Research Institute (J.M., R.J.S., C.L.), Newcastle,
  • Bevan S; From the School of Medicine and Public Health (E.G.H., J.S., M.M., J.A.) and School of Nursing and Midwifery (J.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit (E.G.H., C.O., J.A.), Hunter Medical Research Institute (J.M., R.J.S., C.L.), Newcastle,
  • Maguire J; From the School of Medicine and Public Health (E.G.H., J.S., M.M., J.A.) and School of Nursing and Midwifery (J.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit (E.G.H., C.O., J.A.), Hunter Medical Research Institute (J.M., R.J.S., C.L.), Newcastle,
  • Koblar SA; From the School of Medicine and Public Health (E.G.H., J.S., M.M., J.A.) and School of Nursing and Midwifery (J.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit (E.G.H., C.O., J.A.), Hunter Medical Research Institute (J.M., R.J.S., C.L.), Newcastle,
  • Sturm J; From the School of Medicine and Public Health (E.G.H., J.S., M.M., J.A.) and School of Nursing and Midwifery (J.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit (E.G.H., C.O., J.A.), Hunter Medical Research Institute (J.M., R.J.S., C.L.), Newcastle,
  • Hankey GJ; From the School of Medicine and Public Health (E.G.H., J.S., M.M., J.A.) and School of Nursing and Midwifery (J.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit (E.G.H., C.O., J.A.), Hunter Medical Research Institute (J.M., R.J.S., C.L.), Newcastle,
  • Oldmeadow C; From the School of Medicine and Public Health (E.G.H., J.S., M.M., J.A.) and School of Nursing and Midwifery (J.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit (E.G.H., C.O., J.A.), Hunter Medical Research Institute (J.M., R.J.S., C.L.), Newcastle,
  • McEvoy M; From the School of Medicine and Public Health (E.G.H., J.S., M.M., J.A.) and School of Nursing and Midwifery (J.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit (E.G.H., C.O., J.A.), Hunter Medical Research Institute (J.M., R.J.S., C.L.), Newcastle,
  • Sudlow C; From the School of Medicine and Public Health (E.G.H., J.S., M.M., J.A.) and School of Nursing and Midwifery (J.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit (E.G.H., C.O., J.A.), Hunter Medical Research Institute (J.M., R.J.S., C.L.), Newcastle,
  • Rothwell PM; From the School of Medicine and Public Health (E.G.H., J.S., M.M., J.A.) and School of Nursing and Midwifery (J.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit (E.G.H., C.O., J.A.), Hunter Medical Research Institute (J.M., R.J.S., C.L.), Newcastle,
  • Coresh J; From the School of Medicine and Public Health (E.G.H., J.S., M.M., J.A.) and School of Nursing and Midwifery (J.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit (E.G.H., C.O., J.A.), Hunter Medical Research Institute (J.M., R.J.S., C.L.), Newcastle,
  • Hamet P; From the School of Medicine and Public Health (E.G.H., J.S., M.M., J.A.) and School of Nursing and Midwifery (J.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit (E.G.H., C.O., J.A.), Hunter Medical Research Institute (J.M., R.J.S., C.L.), Newcastle,
  • Tremblay J; From the School of Medicine and Public Health (E.G.H., J.S., M.M., J.A.) and School of Nursing and Midwifery (J.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit (E.G.H., C.O., J.A.), Hunter Medical Research Institute (J.M., R.J.S., C.L.), Newcastle,
  • Turner ST; From the School of Medicine and Public Health (E.G.H., J.S., M.M., J.A.) and School of Nursing and Midwifery (J.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit (E.G.H., C.O., J.A.), Hunter Medical Research Institute (J.M., R.J.S., C.L.), Newcastle,
  • de Andrade M; From the School of Medicine and Public Health (E.G.H., J.S., M.M., J.A.) and School of Nursing and Midwifery (J.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit (E.G.H., C.O., J.A.), Hunter Medical Research Institute (J.M., R.J.S., C.L.), Newcastle,
  • Rao M; From the School of Medicine and Public Health (E.G.H., J.S., M.M., J.A.) and School of Nursing and Midwifery (J.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit (E.G.H., C.O., J.A.), Hunter Medical Research Institute (J.M., R.J.S., C.L.), Newcastle,
  • Schmidt R; From the School of Medicine and Public Health (E.G.H., J.S., M.M., J.A.) and School of Nursing and Midwifery (J.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit (E.G.H., C.O., J.A.), Hunter Medical Research Institute (J.M., R.J.S., C.L.), Newcastle,
  • Crick PA; From the School of Medicine and Public Health (E.G.H., J.S., M.M., J.A.) and School of Nursing and Midwifery (J.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit (E.G.H., C.O., J.A.), Hunter Medical Research Institute (J.M., R.J.S., C.L.), Newcastle,
  • Robino A; From the School of Medicine and Public Health (E.G.H., J.S., M.M., J.A.) and School of Nursing and Midwifery (J.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit (E.G.H., C.O., J.A.), Hunter Medical Research Institute (J.M., R.J.S., C.L.), Newcastle,
  • Peralta CA; From the School of Medicine and Public Health (E.G.H., J.S., M.M., J.A.) and School of Nursing and Midwifery (J.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit (E.G.H., C.O., J.A.), Hunter Medical Research Institute (J.M., R.J.S., C.L.), Newcastle,
  • Jukema JW; From the School of Medicine and Public Health (E.G.H., J.S., M.M., J.A.) and School of Nursing and Midwifery (J.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit (E.G.H., C.O., J.A.), Hunter Medical Research Institute (J.M., R.J.S., C.L.), Newcastle,
  • Mitchell P; From the School of Medicine and Public Health (E.G.H., J.S., M.M., J.A.) and School of Nursing and Midwifery (J.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit (E.G.H., C.O., J.A.), Hunter Medical Research Institute (J.M., R.J.S., C.L.), Newcastle,
  • Rosas SE; From the School of Medicine and Public Health (E.G.H., J.S., M.M., J.A.) and School of Nursing and Midwifery (J.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit (E.G.H., C.O., J.A.), Hunter Medical Research Institute (J.M., R.J.S., C.L.), Newcastle,
  • Wang JJ; From the School of Medicine and Public Health (E.G.H., J.S., M.M., J.A.) and School of Nursing and Midwifery (J.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit (E.G.H., C.O., J.A.), Hunter Medical Research Institute (J.M., R.J.S., C.L.), Newcastle,
  • Scott RJ; From the School of Medicine and Public Health (E.G.H., J.S., M.M., J.A.) and School of Nursing and Midwifery (J.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit (E.G.H., C.O., J.A.), Hunter Medical Research Institute (J.M., R.J.S., C.L.), Newcastle,
  • Dichgans M; From the School of Medicine and Public Health (E.G.H., J.S., M.M., J.A.) and School of Nursing and Midwifery (J.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit (E.G.H., C.O., J.A.), Hunter Medical Research Institute (J.M., R.J.S., C.L.), Newcastle,
  • Mitchell BD; From the School of Medicine and Public Health (E.G.H., J.S., M.M., J.A.) and School of Nursing and Midwifery (J.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit (E.G.H., C.O., J.A.), Hunter Medical Research Institute (J.M., R.J.S., C.L.), Newcastle,
  • Kao WH; From the School of Medicine and Public Health (E.G.H., J.S., M.M., J.A.) and School of Nursing and Midwifery (J.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit (E.G.H., C.O., J.A.), Hunter Medical Research Institute (J.M., R.J.S., C.L.), Newcastle,
  • Fox CS; From the School of Medicine and Public Health (E.G.H., J.S., M.M., J.A.) and School of Nursing and Midwifery (J.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit (E.G.H., C.O., J.A.), Hunter Medical Research Institute (J.M., R.J.S., C.L.), Newcastle,
  • Levi C; From the School of Medicine and Public Health (E.G.H., J.S., M.M., J.A.) and School of Nursing and Midwifery (J.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit (E.G.H., C.O., J.A.), Hunter Medical Research Institute (J.M., R.J.S., C.L.), Newcastle,
  • Attia J; From the School of Medicine and Public Health (E.G.H., J.S., M.M., J.A.) and School of Nursing and Midwifery (J.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit (E.G.H., C.O., J.A.), Hunter Medical Research Institute (J.M., R.J.S., C.L.), Newcastle,
  • Markus HS; From the School of Medicine and Public Health (E.G.H., J.S., M.M., J.A.) and School of Nursing and Midwifery (J.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit (E.G.H., C.O., J.A.), Hunter Medical Research Institute (J.M., R.J.S., C.L.), Newcastle,
Stroke ; 45(12): 3508-13, 2014 Dec.
Article en En | MEDLINE | ID: mdl-25352485
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<0.05 (peak P=0.004) and all showing the epidemiologically expected direction of effect. A similar pattern was observed for polygenic scores reflecting higher urinary albumin to creatinine ratio, of which 3 associated with large artery atherosclerosis (peak P=0.01) and all showed the expected directional association. One urinary albumin to creatinine ratio-based score also associated with small vessel disease (P=0.03). The global pattern of results was unlikely to have occurred by chance (P=0.02). 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Predisposición Genética a la Enfermedad / Accidente Cerebrovascular / Enfermedades Renales Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Stroke Año: 2014 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Predisposición Genética a la Enfermedad / Accidente Cerebrovascular / Enfermedades Renales Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Stroke Año: 2014 Tipo del documento: Article Pais de publicación: Estados Unidos