Polygenic overlap between kidney function and large artery atherosclerotic stroke

Holliday, EG; Traylor, M; Malik, R; Bevan, S; Maguire, J; Koblar, SA; Sturm, J; Hankey, GJ; Oldmeadow, C; McEvoy, M; Sudlow, C; Rothwell, PM; Coresh, J; Hamet, P; Tremblay, J; Turner, ST; De Andrade, M; Rao, M; Schmidt, R; Crick, PA; Robino, A; Peralta, CA; Jukema, JW; Mitchell, P; Rosas, SE; Wang, JJ; Scott, RJ; Dichgans, M; Mitchell, BD; Kao, WHL; Fox, CS; Levi, C; Attia, J; Markus, HS

Polygenic overlap between kidney function and large artery atherosclerotic stroke

Holliday, EG Traylor, M Malik, R Bevan, S Maguire, J

Koblar, SA Sturm, J Hankey, GJ Oldmeadow, C McEvoy, M Sudlow, C Rothwell, PM Coresh, J Hamet, P Tremblay, J Turner, ST De Andrade, M Rao, M Schmidt, R Crick, PA Robino, A Peralta, CA Jukema, JW Mitchell, P Rosas, SE Wang, JJ Scott, RJ Dichgans, M Mitchell, BD Kao, WHL Fox, CS Levi, C Attia, J Markus, HS

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Publication Type:: Journal Article
Citation:: Stroke, 2014, 45 (12), pp. 3508 - 3513
Issue Date:: 2014-12-11

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Field	Value	Language
dc.contributor.author	Holliday, EG	en_US
dc.contributor.author	Traylor, M	en_US
dc.contributor.author	Malik, R	en_US
dc.contributor.author	Bevan, S	en_US
dc.contributor.author	Maguire, J https://orcid.org/0000-0001-5722-8311	en_US
dc.contributor.author	Koblar, SA	en_US
dc.contributor.author	Sturm, J	en_US
dc.contributor.author	Hankey, GJ	en_US
dc.contributor.author	Oldmeadow, C	en_US
dc.contributor.author	McEvoy, M	en_US
dc.contributor.author	Sudlow, C	en_US
dc.contributor.author	Rothwell, PM	en_US
dc.contributor.author	Coresh, J	en_US
dc.contributor.author	Hamet, P	en_US
dc.contributor.author	Tremblay, J	en_US
dc.contributor.author	Turner, ST	en_US
dc.contributor.author	De Andrade, M	en_US
dc.contributor.author	Rao, M	en_US
dc.contributor.author	Schmidt, R	en_US
dc.contributor.author	Crick, PA	en_US
dc.contributor.author	Robino, A	en_US
dc.contributor.author	Peralta, CA	en_US
dc.contributor.author	Jukema, JW	en_US
dc.contributor.author	Mitchell, P	en_US
dc.contributor.author	Rosas, SE	en_US
dc.contributor.author	Wang, JJ	en_US
dc.contributor.author	Scott, RJ	en_US
dc.contributor.author	Dichgans, M	en_US
dc.contributor.author	Mitchell, BD	en_US
dc.contributor.author	Kao, WHL	en_US
dc.contributor.author	Fox, CS	en_US
dc.contributor.author	Levi, C	en_US
dc.contributor.author	Attia, J	en_US
dc.contributor.author	Markus, HS	en_US
dc.date.issued	2014-12-11	en_US
dc.identifier.citation	Stroke, 2014, 45 (12), pp. 3508 - 3513	en_US
dc.identifier.issn	0039-2499	en_US
dc.identifier.uri	http://hdl.handle.net/10453/118883
dc.description.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<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.	en_US
dc.relation.ispartof	Stroke	en_US
dc.relation.isbasedon	10.1161/STROKEAHA.114.006609	en_US
dc.subject.classification	Neurology & Neurosurgery	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Kidney Diseases	en_US
dc.subject.mesh	Albuminuria	en_US
dc.subject.mesh	Genetic Predisposition to Disease	en_US
dc.subject.mesh	Genome-Wide Association Study	en_US
dc.subject.mesh	Genotype	en_US
dc.subject.mesh	Polymorphism, Single Nucleotide	en_US
dc.subject.mesh	Stroke	en_US
dc.title	Polygenic overlap between kidney function and large artery atherosclerotic stroke	en_US
dc.type	Journal Article
utslib.citation.volume	12	en_US
utslib.citation.volume	45	en_US
utslib.for	1102 Cardiorespiratory Medicine and Haematology	en_US
utslib.for	1103 Clinical Sciences	en_US
utslib.for	1109 Neurosciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Health
utslib.copyright.status	closed_access
pubs.issue	12	en_US
pubs.publication-status	Published	en_US
pubs.volume	45	en_US

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<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.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/118883