Your browser doesn't support javascript.
loading
Common Genetic Variation Indicates Separate Causes for Periventricular and Deep White Matter Hyperintensities.
Armstrong, Nicola J; Mather, Karen A; Sargurupremraj, Muralidharan; Knol, Maria J; Malik, Rainer; Satizabal, Claudia L; Yanek, Lisa R; Wen, Wei; Gudnason, Vilmundur G; Dueker, Nicole D; Elliott, Lloyd T; Hofer, Edith; Bis, Joshua; Jahanshad, Neda; Li, Shuo; Logue, Mark A; Luciano, Michelle; Scholz, Markus; Smith, Albert V; Trompet, Stella; Vojinovic, Dina; Xia, Rui; Alfaro-Almagro, Fidel; Ames, David; Amin, Najaf; Amouyel, Philippe; Beiser, Alexa S; Brodaty, Henry; Deary, Ian J; Fennema-Notestine, Christine; Gampawar, Piyush G; Gottesman, Rebecca; Griffanti, Ludovica; Jack, Clifford R; Jenkinson, Mark; Jiang, Jiyang; Kral, Brian G; Kwok, John B; Lampe, Leonie; C M Liewald, David; Maillard, Pauline; Marchini, Jonathan; Bastin, Mark E; Mazoyer, Bernard; Pirpamer, Lukas; Rafael Romero, José; Roshchupkin, Gennady V; Schofield, Peter R; Schroeter, Matthias L; Stott, David J.
Afiliação
  • Armstrong NJ; Mathematics and Statistics, Murdoch University, Perth, Australia (N.J.A.).
  • Mather KA; Centre for Healthy Brain Ageing, School of Psychiatry (K.A.M., W.W., H.B., J.J., A.T., J.T., P.S.S.), University of New South Wales, Sydney, Australia.
  • Sargurupremraj M; Neuroscience Research Australia, Sydney, Australia (K.A.M., P.R.S., A.T.).
  • Knol MJ; University Bordeaux, Inserm, Bordeaux Population Health Research Center, France (M.S., C.T., S.D.).
  • Malik R; Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands (M.J.K., D.V., N.A., G.V.R., M.W.V., C.M.v.D., M.A.I., H.H.H.A.).
  • Satizabal CL; Institute for Stroke and Dementia Research (ISD), University Hospital, Ludwig-Maximilians-Universität LMU Munich, Germany (R.M., M.D.).
  • Yanek LR; Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, UT Health San Antonio, San Antonio, TX (C.L.S., S.S.).
  • Wen W; The Framingham Heart Study, MA (C.L.S., A.S.B., J.R.R., S.S.).
  • Gudnason VG; Department of Neurology (C.L.S., A.S.B., J.R.R., S.S.), Boston University School of Medicine, MA.
  • Dueker ND; GeneSTAR Research Program (L.R.Y., B.G.K., L.C.B., P.A.N.), Johns Hopkins University School of Medicine, Baltimore, MD.
  • Elliott LT; Centre for Healthy Brain Ageing, School of Psychiatry (K.A.M., W.W., H.B., J.J., A.T., J.T., P.S.S.), University of New South Wales, Sydney, Australia.
  • Hofer E; Icelandic Heart Association, Kopavogur (V.G.G., S.S.).
  • Bis J; University of Iceland, Reykjavik, Iceland (V.G.G., A.V.S.).
  • Jahanshad N; Dr. John T. Macdonald Foundation Department of Human Genetics (R.L.S.), University of Miami, FL.
  • Li S; Department of Statistics and Actuarial Science, Simon Fraser University, Burnaby, BC, Canada (L.T.E.).
  • Logue MA; Wellcome Centre for Integrative Neuroimaging (WIN FMRIB) (L.T.E., F.A.-A., L.G., M.J., S.M.S.), University of Oxford, United Kingdom.
  • Luciano M; Clinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Austria (E.H., R.S.).
  • Scholz M; Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Austria (E.H.).
  • Smith AV; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA (J.B., B.P., W.L.).
  • Trompet S; Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, University of Southern California, Marina del Rey (N.J., P.M.T.).
  • Vojinovic D; Department of Biostatistics, Boston University School of Public Health, Boston, MA (S.L., M.A.L., A.S.B., Q.Y.).
  • Xia R; Department of Psychiatry and Biomedical Genetics Section (M.A.L.), Boston University School of Medicine, MA.
  • Alfaro-Almagro F; Department of Biostatistics, Boston University School of Public Health, Boston, MA (S.L., M.A.L., A.S.B., Q.Y.).
  • Ames D; National Center for PTSD: Behavioral Science Division, VA Boston Healthcare System, Boston, MA (M.A.L.).
  • Amin N; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, United Kingdom (M.L., I.J.D., D.C.M.L., M.E.B., J.M.W.).
  • Amouyel P; Institute for Medical Informatics, Statistics and Epidemiology (M.S.).
  • Beiser AS; University of Iceland, Reykjavik, Iceland (V.G.G., A.V.S.).
  • Brodaty H; Department of Internal Medicine, Section of Gerontology and Geriatrics (S.T.), Leiden University Medical Center, the Netherlands.
  • Deary IJ; Department of Cardiology (S.T.), Leiden University Medical Center, the Netherlands.
  • Fennema-Notestine C; Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands (M.J.K., D.V., N.A., G.V.R., M.W.V., C.M.v.D., M.A.I., H.H.H.A.).
  • Gampawar PG; Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, TX (R.X., M.F.).
  • Gottesman R; Wellcome Centre for Integrative Neuroimaging (WIN FMRIB) (L.T.E., F.A.-A., L.G., M.J., S.M.S.), University of Oxford, United Kingdom.
  • Griffanti L; National Ageing Research Institute, Parkville, Victoria, Australia (D.A.).
  • Jack CR; Academic Unit for Psychiatry of Old Age, University of Melbourne, St George's Hospital, Kew, Australia (D.A.).
  • Jenkinson M; Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands (M.J.K., D.V., N.A., G.V.R., M.W.V., C.M.v.D., M.A.I., H.H.H.A.).
  • Jiang J; Lille University, Inserm, Institut Pasteur de Lille, RID-AGE - Risk Factors and Molecular Determinants of Aging-Related Diseases and Labex Distalz, France (P.A.).
  • Kral BG; Lille University, Inserm, CHU Lille, Institut Pasteur de Lille, RID-AGE (P.A.).
  • Kwok JB; The Framingham Heart Study, MA (C.L.S., A.S.B., J.R.R., S.S.).
  • Lampe L; Department of Neurology (C.L.S., A.S.B., J.R.R., S.S.), Boston University School of Medicine, MA.
  • C M Liewald D; Department of Biostatistics, Boston University School of Public Health, Boston, MA (S.L., M.A.L., A.S.B., Q.Y.).
  • Maillard P; Centre for Healthy Brain Ageing, School of Psychiatry (K.A.M., W.W., H.B., J.J., A.T., J.T., P.S.S.), University of New South Wales, Sydney, Australia.
  • Marchini J; Dementia Centre for Research Collaboration (H.B.), University of New South Wales, Sydney, Australia.
  • Bastin ME; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, United Kingdom (M.L., I.J.D., D.C.M.L., M.E.B., J.M.W.).
  • Mazoyer B; Department of Psychiatry (C.F.-N.), University of California, San Diego, La Jolla, CA.
  • Pirpamer L; Center for Behavior Genetics of Aging (C.F.-N.), University of California, San Diego, La Jolla, CA.
  • Rafael Romero J; Gottfried Schatz Research Center (for Cell Signaling, Metabolism and Aging), Medical University of Graz, Austria (P.G.G., H.S.).
  • Roshchupkin GV; Department of Neurology, Cerebrovascular and stroke Division (R.G.), Johns Hopkins University School of Medicine, Baltimore, MD.
  • Schofield PR; Wellcome Centre for Integrative Neuroimaging (WIN FMRIB) (L.T.E., F.A.-A., L.G., M.J., S.M.S.), University of Oxford, United Kingdom.
  • Schroeter ML; Department of Radiology, Mayo Clinic, Rochester, MN (C.R.J.J.).
  • Stott DJ; Wellcome Centre for Integrative Neuroimaging (WIN FMRIB) (L.T.E., F.A.-A., L.G., M.J., S.M.S.), University of Oxford, United Kingdom.
Stroke ; 51(7): 2111-2121, 2020 07.
Article em En | MEDLINE | ID: mdl-32517579
ABSTRACT
BACKGROUND AND

PURPOSE:

Periventricular white matter hyperintensities (WMH; PVWMH) and deep WMH (DWMH) are regional classifications of WMH and reflect proposed differences in cause. In the first study, to date, we undertook genome-wide association analyses of DWMH and PVWMH to show that these phenotypes have different genetic underpinnings.

METHODS:

Participants were aged 45 years and older, free of stroke and dementia. We conducted genome-wide association analyses of PVWMH and DWMH in 26,654 participants from CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology), ENIGMA (Enhancing Neuro-Imaging Genetics Through Meta-Analysis), and the UKB (UK Biobank). Regional correlations were investigated using the genome-wide association analyses -pairwise method. Cross-trait genetic correlations between PVWMH, DWMH, stroke, and dementia were estimated using LDSC.

RESULTS:

In the discovery and replication analysis, for PVWMH only, we found associations on chromosomes 2 (NBEAL), 10q23.1 (TSPAN14/FAM231A), and 10q24.33 (SH3PXD2A). In the much larger combined meta-analysis of all cohorts, we identified ten significant regions for PVWMH chromosomes 2 (3 regions), 6, 7, 10 (2 regions), 13, 16, and 17q23.1. New loci of interest include 7q36.1 (NOS3) and 16q24.2. In both the discovery/replication and combined analysis, we found genome-wide significant associations for the 17q25.1 locus for both DWMH and PVWMH. Using gene-based association analysis, 19 genes across all regions were identified for PVWMH only, including the new genes CALCRL (2q32.1), KLHL24 (3q27.1), VCAN (5q27.1), and POLR2F (22q13.1). Thirteen genes in the 17q25.1 locus were significant for both phenotypes. More extensive genetic correlations were observed for PVWMH with small vessel ischemic stroke. There were no associations with dementia for either phenotype.

CONCLUSIONS:

Our study confirms these phenotypes have distinct and also shared genetic architectures. Genetic analyses indicated PVWMH was more associated with ischemic stroke whilst DWMH loci were implicated in vascular, astrocyte, and neuronal function. Our study confirms these phenotypes are distinct neuroimaging classifications and identifies new candidate genes associated with PVWMH only.
Assuntos
Palavras-chave
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Encéfalo / Predisposição Genética para Doença / Doenças de Pequenos Vasos Cerebrais / Substância Branca Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Stroke Ano de publicação: 2020 Tipo de documento: Article
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Encéfalo / Predisposição Genética para Doença / Doenças de Pequenos Vasos Cerebrais / Substância Branca Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Stroke Ano de publicação: 2020 Tipo de documento: Article