Genetic overlap and causal inferences between kidney function and cerebrovascular disease.

Cerebral Small Vessel Diseases / genetics Cerebrovascular Disorders / genetics Genetic Predisposition to Disease Genome-Wide Association Study Glomerular Filtration Rate Humans Kidney / physiopathology Kidney Function Tests Linkage Disequilibrium Magnetic Resonance Imaging Multifactorial Inheritance Renal Insufficiency, Chronic / complications Risk Assessment Stroke / physiopathology

Journal

Neurology
ISSN: 1526-632X
Titre abrégé: Neurology
Pays: United States
ID NLM: 0401060

Informations de publication

Date de publication:
16 06 2020
Historique:
received: 15 05 2019
accepted: 26 01 2020
pubmed: 23 5 2020
medline: 22 9 2020
entrez: 23 5 2020
Statut: ppublish

Résumé

Leveraging large-scale genetic data, we aimed to identify shared pathogenic mechanisms and causal relationships between impaired kidney function and cerebrovascular disease phenotypes. We used summary statistics from genome-wide association studies (GWAS) of kidney function traits (chronic kidney disease diagnosis, estimated glomerular filtration rate [eGFR], and urinary albumin-to-creatinine ratio [UACR]) and cerebrovascular disease phenotypes (ischemic stroke and its subtypes, intracerebral hemorrhage [ICH], and white matter hyperintensities [WMH] on brain MRI). We (1) tested the genetic overlap between them with polygenic risk scores (PRS), (2) searched for common pleiotropic loci with pairwise GWAS analyses, and (3) explored causal associations by employing 2-sample Mendelian randomization. A PRS for lower eGFR was associated with higher large artery stroke (LAS) risk ( Impaired kidney function, as assessed by decreased eGFR and increased UACR, may be causally involved in the pathogenesis of LAS. Increased UACR, previously proposed as a marker of systemic small vessel disease, is involved in ICH risk and shares a genetic risk factor at 2q33 with manifestations of cerebral small vessel disease.

Identifiants

DOI: 10.1212/WNL.0000000000009642 PMID: 32439819 PMC: PMC7455337
pubmed: 32439819
pii: WNL.0000000000009642
doi: 10.1212/WNL.0000000000009642
pmc: PMC7455337
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e2581-e2591

Subventions

Organisme : NINDS NIH HHS
ID : K23 NS086873
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS093870
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS103924
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2020 American Academy of Neurology.

Références

Diabetes Spectr. 2015 Aug;28(3):162-6
pubmed: 26300608
Nat Genet. 2019 Jan;51(1):51-62
pubmed: 30578418
Stroke. 2014 Dec;45(12):3508-13
pubmed: 25352485
N Engl J Med. 2018 Dec 20;379(25):2429-2437
pubmed: 30575491
Nat Genet. 2018 May;50(5):693-698
pubmed: 29686387
Nat Genet. 2017 Sep;49(9):1385-1391
pubmed: 28714975
Am J Hum Genet. 2018 Oct 4;103(4):461-473
pubmed: 30220432
Nat Commun. 2016 Jan 21;7:10023
pubmed: 26831199
Stroke. 1993 Jan;24(1):35-41
pubmed: 7678184
Nat Genet. 2018 Apr;50(4):524-537
pubmed: 29531354
Nat Genet. 1996 Nov;14(3):269-76
pubmed: 8896555
Am J Hum Genet. 2018 Jun 7;102(6):1185-1194
pubmed: 29754766
Sci Rep. 2017 Apr 28;7:45040
pubmed: 28452372
Curr Opin Nephrol Hypertens. 2014 May;23(3):298-305
pubmed: 24662984
Nature. 2012 Nov 1;491(7422):56-65
pubmed: 23128226
Lancet. 2010 Jun 12;375(9731):2073-81
pubmed: 20483451
BMJ. 2018 Jul 12;362:k601
pubmed: 30002074
Lancet Neurol. 2014 Aug;13(8):823-33
pubmed: 25030514
Neurology. 2016 Jan 12;86(2):146-53
pubmed: 26674333
Int J Epidemiol. 2003 Feb;32(1):1-22
pubmed: 12689998
N Engl J Med. 2004 Sep 23;351(13):1296-305
pubmed: 15385656
BMJ. 2010 Sep 30;341:c4249
pubmed: 20884696
Nat Genet. 2015 Nov;47(11):1236-41
pubmed: 26414676
Am J Hum Genet. 2014 Apr 3;94(4):511-21
pubmed: 24656865
Front Cardiovasc Med. 2018 May 28;5:51
pubmed: 29892602
J Am Geriatr Soc. 2018 Mar;66(3):509-517
pubmed: 29372928
Diabetes. 2016 Mar;65(3):803-17
pubmed: 26631737
Nat Genet. 2016 Jul;48(7):709-17
pubmed: 27182965
Nat Genet. 2019 Feb;51(2):277-284
pubmed: 30510236
Nat Commun. 2018 Nov 14;9(1):4774
pubmed: 30429480
N Engl J Med. 2012 Jul 5;367(1):20-9
pubmed: 22762315
PLoS Genet. 2012;8(3):e1002607
pubmed: 22479202
Sci Rep. 2018 May 8;8(1):7102
pubmed: 29740026
Neurology. 2012 Jun 12;78(24):1909-15
pubmed: 22592359
Heart. 2017 Sep;103(18):1400-1407
pubmed: 28596306
Lancet Neurol. 2010 Jul;9(7):689-701
pubmed: 20610345
Am J Kidney Dis. 2008 Mar;51(3):395-406
pubmed: 18295055
Lancet. 2012 Aug 11;380(9841):572-80
pubmed: 22607825
Am J Med Genet A. 2003 Feb 15;117A(1):10-7
pubmed: 12548734
Nat Genet. 2018 Oct;50(10):1412-1425
pubmed: 30224653
J Am Soc Nephrol. 2017 Mar;28(3):981-994
pubmed: 27920155
Stroke. 2018 Jun;49(6):1340-1347
pubmed: 29752348
Circ Cardiovasc Genet. 2015 Apr;8(2):398-409
pubmed: 25663218
Curr Epidemiol Rep. 2017;4(4):330-345
pubmed: 29226067
Neurology. 2009 Dec 1;73(22):1858-65
pubmed: 19949032
J Am Soc Nephrol. 2004 May;15(5):1307-15
pubmed: 15100371
N Engl J Med. 2013 Sep 5;369(10):932-43
pubmed: 24004120

Auteurs

Sandro Marini (S)

From the Center for Genomic Medicine (S.M., J.C., J.Q.A.H., J.R., C.D.A.), Department of Neurology (J.R., C.D.A.), and Henry and Allison McCance Center for Brain Health (J.R., C.D.A.), Massachusetts General Hospital, Boston; Institute for Stroke and Dementia Research (M.K.G., M.D., R.M.), University Hospital of Ludwig-Maximilians-University; Graduate School for Systemic Neurosciences (M.K.G.), Ludwig-Maximilians-University, Munich, Germany; Department of Medicine (Biomedical Genetics) (J.C.), Boston University School of Medicine, MA; Munich Cluster for Systems Neurology (SyNergy) (M.D.); German Centre for Neurodegenerative Diseases (DZNE) (M.D.), Munich, Germany; and Program in Medical and Population Genetics (J.R., C.D.A.), Broad Institute of Harvard and MIT, Cambridge, MA. sandro.marini08@gmail.com.

Marios K Georgakis (MK)

From the Center for Genomic Medicine (S.M., J.C., J.Q.A.H., J.R., C.D.A.), Department of Neurology (J.R., C.D.A.), and Henry and Allison McCance Center for Brain Health (J.R., C.D.A.), Massachusetts General Hospital, Boston; Institute for Stroke and Dementia Research (M.K.G., M.D., R.M.), University Hospital of Ludwig-Maximilians-University; Graduate School for Systemic Neurosciences (M.K.G.), Ludwig-Maximilians-University, Munich, Germany; Department of Medicine (Biomedical Genetics) (J.C.), Boston University School of Medicine, MA; Munich Cluster for Systems Neurology (SyNergy) (M.D.); German Centre for Neurodegenerative Diseases (DZNE) (M.D.), Munich, Germany; and Program in Medical and Population Genetics (J.R., C.D.A.), Broad Institute of Harvard and MIT, Cambridge, MA.

Jaeyoon Chung (J)

From the Center for Genomic Medicine (S.M., J.C., J.Q.A.H., J.R., C.D.A.), Department of Neurology (J.R., C.D.A.), and Henry and Allison McCance Center for Brain Health (J.R., C.D.A.), Massachusetts General Hospital, Boston; Institute for Stroke and Dementia Research (M.K.G., M.D., R.M.), University Hospital of Ludwig-Maximilians-University; Graduate School for Systemic Neurosciences (M.K.G.), Ludwig-Maximilians-University, Munich, Germany; Department of Medicine (Biomedical Genetics) (J.C.), Boston University School of Medicine, MA; Munich Cluster for Systems Neurology (SyNergy) (M.D.); German Centre for Neurodegenerative Diseases (DZNE) (M.D.), Munich, Germany; and Program in Medical and Population Genetics (J.R., C.D.A.), Broad Institute of Harvard and MIT, Cambridge, MA.

Jonathan Q A Henry (JQA)

From the Center for Genomic Medicine (S.M., J.C., J.Q.A.H., J.R., C.D.A.), Department of Neurology (J.R., C.D.A.), and Henry and Allison McCance Center for Brain Health (J.R., C.D.A.), Massachusetts General Hospital, Boston; Institute for Stroke and Dementia Research (M.K.G., M.D., R.M.), University Hospital of Ludwig-Maximilians-University; Graduate School for Systemic Neurosciences (M.K.G.), Ludwig-Maximilians-University, Munich, Germany; Department of Medicine (Biomedical Genetics) (J.C.), Boston University School of Medicine, MA; Munich Cluster for Systems Neurology (SyNergy) (M.D.); German Centre for Neurodegenerative Diseases (DZNE) (M.D.), Munich, Germany; and Program in Medical and Population Genetics (J.R., C.D.A.), Broad Institute of Harvard and MIT, Cambridge, MA.

Martin Dichgans (M)

From the Center for Genomic Medicine (S.M., J.C., J.Q.A.H., J.R., C.D.A.), Department of Neurology (J.R., C.D.A.), and Henry and Allison McCance Center for Brain Health (J.R., C.D.A.), Massachusetts General Hospital, Boston; Institute for Stroke and Dementia Research (M.K.G., M.D., R.M.), University Hospital of Ludwig-Maximilians-University; Graduate School for Systemic Neurosciences (M.K.G.), Ludwig-Maximilians-University, Munich, Germany; Department of Medicine (Biomedical Genetics) (J.C.), Boston University School of Medicine, MA; Munich Cluster for Systems Neurology (SyNergy) (M.D.); German Centre for Neurodegenerative Diseases (DZNE) (M.D.), Munich, Germany; and Program in Medical and Population Genetics (J.R., C.D.A.), Broad Institute of Harvard and MIT, Cambridge, MA.

Jonathan Rosand (J)

From the Center for Genomic Medicine (S.M., J.C., J.Q.A.H., J.R., C.D.A.), Department of Neurology (J.R., C.D.A.), and Henry and Allison McCance Center for Brain Health (J.R., C.D.A.), Massachusetts General Hospital, Boston; Institute for Stroke and Dementia Research (M.K.G., M.D., R.M.), University Hospital of Ludwig-Maximilians-University; Graduate School for Systemic Neurosciences (M.K.G.), Ludwig-Maximilians-University, Munich, Germany; Department of Medicine (Biomedical Genetics) (J.C.), Boston University School of Medicine, MA; Munich Cluster for Systems Neurology (SyNergy) (M.D.); German Centre for Neurodegenerative Diseases (DZNE) (M.D.), Munich, Germany; and Program in Medical and Population Genetics (J.R., C.D.A.), Broad Institute of Harvard and MIT, Cambridge, MA.

Rainer Malik (R)

From the Center for Genomic Medicine (S.M., J.C., J.Q.A.H., J.R., C.D.A.), Department of Neurology (J.R., C.D.A.), and Henry and Allison McCance Center for Brain Health (J.R., C.D.A.), Massachusetts General Hospital, Boston; Institute for Stroke and Dementia Research (M.K.G., M.D., R.M.), University Hospital of Ludwig-Maximilians-University; Graduate School for Systemic Neurosciences (M.K.G.), Ludwig-Maximilians-University, Munich, Germany; Department of Medicine (Biomedical Genetics) (J.C.), Boston University School of Medicine, MA; Munich Cluster for Systems Neurology (SyNergy) (M.D.); German Centre for Neurodegenerative Diseases (DZNE) (M.D.), Munich, Germany; and Program in Medical and Population Genetics (J.R., C.D.A.), Broad Institute of Harvard and MIT, Cambridge, MA.

Christopher D Anderson (CD)

From the Center for Genomic Medicine (S.M., J.C., J.Q.A.H., J.R., C.D.A.), Department of Neurology (J.R., C.D.A.), and Henry and Allison McCance Center for Brain Health (J.R., C.D.A.), Massachusetts General Hospital, Boston; Institute for Stroke and Dementia Research (M.K.G., M.D., R.M.), University Hospital of Ludwig-Maximilians-University; Graduate School for Systemic Neurosciences (M.K.G.), Ludwig-Maximilians-University, Munich, Germany; Department of Medicine (Biomedical Genetics) (J.C.), Boston University School of Medicine, MA; Munich Cluster for Systems Neurology (SyNergy) (M.D.); German Centre for Neurodegenerative Diseases (DZNE) (M.D.), Munich, Germany; and Program in Medical and Population Genetics (J.R., C.D.A.), Broad Institute of Harvard and MIT, Cambridge, MA.

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Classifications MeSH

questionsmedicales.fr › Maladies cardiovasculaires › Maladies vasculaires › Angiopathies intracrâniennes › Maladies des petits vaisseaux cérébraux › Genetic overlap and causal inferences between...
questionsmedicales.fr › Maladies cardiovasculaires › Maladies vasculaires › Angiopathies intracrâniennes › Genetic overlap and causal inferences between...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Prédisposition génétique à une maladie › Genetic overlap and causal inferences between...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › Genetic overlap and causal inferences between...
questionsmedicales.fr › Phénomènes physiologiques des appareils urinaire et reproducteur › Phénomènes physiologiques des voies urinaires › Débit de filtration glomérulaire › Genetic overlap and causal inferences between...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Genetic overlap and causal inferences between...
questionsmedicales.fr › Appareil urogénital › Voies urinaires › Rein › Genetic overlap and causal inferences between...
questionsmedicales.fr › Diagnostic › Techniques et procédures diagnostiques › Techniques de diagnostic urologique › Tests de la fonction rénale › Genetic overlap and causal inferences between...
questionsmedicales.fr › Phénomènes génétiques › Liaison génétique › Déséquilibre de liaison › Genetic overlap and causal inferences between...
questionsmedicales.fr › Diagnostic › Techniques et procédures diagnostiques › Imagerie diagnostique › Tomographie › Imagerie par résonance magnétique › Genetic overlap and causal inferences between...
questionsmedicales.fr › Phénomènes génétiques › Modes de transmission héréditaire › Hérédité multifactorielle › Genetic overlap and causal inferences between...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Maladie chronique › Insuffisance rénale chronique › Genetic overlap and causal inferences between...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Probabilité › Risque › Appréciation des risques › Genetic overlap and causal inferences between...
questionsmedicales.fr › Maladies cardiovasculaires › Maladies vasculaires › Angiopathies intracrâniennes › Accident vasculaire cérébral › Genetic overlap and causal inferences between...