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Genome-wide study o...
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Hop, Paul J.Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, Netherlands
(author)
Genome-wide study of DNA methylation shows alterations in metabolic, inflammatory, and cholesterol pathways in ALS
- Article/chapterEnglish2022
Publisher, publication year, extent ...
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American Association for the Advancement of Science,2022
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:umu-194403
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https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-194403URI
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https://doi.org/10.1126/scitranslmed.abj0264DOI
Supplementary language notes
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Language:English
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Summary in:English
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Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability between 40 and 50%. DNA methylation patterns can serve as proxies of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide association study meta-analysis in 9706 samples passing stringent quality control (6763 patients, 2943 controls). We identified a total of 45 differentially methylated positions (DMPs) annotated to 42 genes, which are enriched for pathways and traits related to metabolism, cholesterol biosynthesis, and immunity. We then tested 39 DNA methylation-based proxies of putative ALS risk factors and found that high-density lipoprotein cholesterol, body mass index, white blood cell proportions, and alcohol intake were independently associated with ALS. Integration of these results with our latest genome-wide association study showed that cholesterol biosynthesis was potentially causally related to ALS. Last, DNA methylation at several DMPs and blood cell proportion estimates derived from DNA methylation data were associated with survival rate in patients, suggesting that they might represent indicators of underlying disease processes potentially amenable to therapeutic interventions.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Zwamborn, Ramona A.J.Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, Netherlands
(author)
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Hannon, EilisUniversity of Exeter Medical School, College of Medicine and Health, University of Exeter, Exeter, United Kingdom
(author)
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Shireby, Gemma L.University of Exeter Medical School, College of Medicine and Health, University of Exeter, Exeter, United Kingdom
(author)
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Nabais, Marta F.University of Exeter Medical School, College of Medicine and Health, University of Exeter, Exeter, United Kingdom; Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia
(author)
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Walker, Emma M.University of Exeter Medical School, College of Medicine and Health, University of Exeter, Exeter, United Kingdom
(author)
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van Rheenen, WouterDepartment of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, Netherlands
(author)
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van Vugt, Joke J.F.A.Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, Netherlands
(author)
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Dekker, Annelot M.Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, Netherlands
(author)
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Westeneng, Henk-JanDepartment of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, Netherlands
(author)
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Tazelaar, Gijs H.P.Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, Netherlands
(author)
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van Eijk, Kristel R.Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, Netherlands
(author)
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Moisse, MatthieuKU Leuven, University of Leuven, Department of Neurosciences, Experimental Neurology and Leuven Brain Institute (LBI), Leuven, Belgium; VIB, Center for Brain and Disease Research, Leuven, Belgium; University Hospitals Leuven, Department of Neurology, Leuven, Belgium
(author)
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Baird, DenisTranslational Biology, Biogen, MA, Boston, United States; MRC Integrative Epidemiology Unit (IEU), Population Health Sciences, University of Bristol, Bristol, United Kingdom
(author)
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Al Khleifat, AhmadMaurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
(author)
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Iacoangeli, AlfredoMaurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; National Institute for Health Research Biomedical Research Centre, Dementia Unit, South London and Maudsley NHS Foundation Trust, King's College London, London, United Kingdom
(author)
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Ticozzi, NicolaDepartment of Neurology-Stroke Unit, Laboratory of Neuroscience, Istituto Auxologico Italiano IRCCS, Milan, Italy; Department of Pathophysiology and Transplantation, “Dino Ferrari” Center, Università degli Studi di Milano, Milan, Italy
(author)
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Ratti, AntoniaDepartment of Neurology-Stroke Unit, Laboratory of Neuroscience, Istituto Auxologico Italiano IRCCS, Milan, Italy; Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, Milano, Italy
(author)
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Cooper-Knock, JonathanSheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, United Kingdom
(author)
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Morrison, Karen E.School of Medicine, Dentistry, and Biomedical Sciences, Queen's University Belfast, Belfast, United Kingdom
(author)
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Shaw, Pamela J.Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, United Kingdom
(author)
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Basak, A. NazliKoc University, School of Medicine, Translational Medicine Research Center, NDAL, Istanbul, Turkey
(author)
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Chiò, Adriano“Rita Levi Montalcini” Department of Neuroscience, ALS Centre, University of Torino, Turin, Italy; Azienda Ospedaliero-Universitaria Città della Salute e della Scienza, SC Neurologia 1U, Turin, Italy
(author)
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Calvo, Andrea“Rita Levi Montalcini” Department of Neuroscience, ALS Centre, University of Torino, Turin, Italy; Azienda Ospedaliero-Universitaria Città della Salute e della Scienza, SC Neurologia 1U, Turin, Italy
(author)
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Moglia, Cristina“Rita Levi Montalcini” Department of Neuroscience, ALS Centre, University of Torino, Turin, Italy; Azienda Ospedaliero-Universitaria Città della Salute e della Scienza, SC Neurologia 1U, Turin, Italy
(author)
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Canosa, Antonio“Rita Levi Montalcini” Department of Neuroscience, ALS Centre, University of Torino, Turin, Italy; Azienda Ospedaliero-Universitaria Città della Salute e della Scienza, SC Neurologia 1U, Turin, Italy
(author)
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Brunetti, Maura“Rita Levi Montalcini” Department of Neuroscience, ALS Centre, University of Torino, Turin, Italy
(author)
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Grassano, Maurizio“Rita Levi Montalcini” Department of Neuroscience, ALS Centre, University of Torino, Turin, Italy
(author)
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Gotkine, MarcFaculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel; Agnes Ginges Center for Human Neurogenetics, Department of Neurology, Hadassah Medical Center, Jerusalem, Israel
(author)
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Lerner, YossefFaculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel; Agnes Ginges Center for Human Neurogenetics, Department of Neurology, Hadassah Medical Center, Jerusalem, Israel
(author)
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Zabari, MichalFaculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel; Agnes Ginges Center for Human Neurogenetics, Department of Neurology, Hadassah Medical Center, Jerusalem, Israel
(author)
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Vourc'H, PatrickService de Biochimie et Biologie moléculaire, CHU de Tours, Tours, France; UMR 1253, Université de Tours, Inserm, Tours, France
(author)
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Corcia, PhilippeUMR 1253, Université de Tours, Inserm, Tours, France; Centre de référence sur la SLA, CHU de Tours, Tours, France
(author)
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Couratier, PhilippeCentre de référence sur la SLA, CHRU de Limoges, Limoges, France; UMR 1094, Université de Limoges, Inserm, Limoges, France
(author)
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Mora Pardina, Jesus S.ALS Unit, Hospital San Rafael, Madrid, Spain
(author)
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Salas, TeresaDepartment of Neurology, Hospital La Paz-Carlos III, Madrid, Spain
(author)
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Dion, PatrickMontréal Neurological Institute and Hospital, McGill University, QC, Montréal, Canada
(author)
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Ross, Jay P.Montréal Neurological Institute and Hospital, McGill University, QC, Montréal, Canada; Department of Human Genetics, McGill University, QC, Montréal, Canada
(author)
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Henderson, Robert D.Department of Neurology, Royal Brisbane and Women's Hospital, QLD, Brisbane, Australia
(author)
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Mathers, SusanCalvary Health Care Bethlehem, VIC, Parkdale, Australia
(author)
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McCombe, Pamela A.Centre for Clinical Research, University of Queensland, QLD, Brisbane, Australia
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Needham, MerrileeFiona Stanley Hospital, WA, Perth, Australia; Notre Dame University, WA, Fremantle, Australia; Institute for Immunology and Infectious Diseases, Murdoch University, WA, Perth, Australia
(author)
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Nicholson, GarthANZAC Research Institute, Concord Repatriation General Hospital, NSW, Sydney, Australia
(author)
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Rowe, Dominic B.Centre for Motor Neuron Disease Research, Macquarie University, NSW, Australia
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Pamphlett, RogerDiscipline of Pathology, Department of Neuropathology, Brain and Mind Centre, University of Sydney, NSW, Sydney, Australia
(author)
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Mather, Karen A.Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, NSW, Sydney, Australia; Neuroscience Research Australia Institute, NSW, Randwick, Australia
(author)
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Sachdev, Perminder S.Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, NSW, Sydney, Australia; Neuropsychiatric Institute, Prince of Wales Hospital, UNSW, NSW, Randwick, Australia
(author)
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Furlong, SarahCentre for Motor Neuron Disease Research, Macquarie University, NSW, Australia
(author)
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Garton, Fleur C.Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia
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Henders, Anjali K.Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia
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Lin, TianInstitute for Molecular Bioscience, University of Queensland, Brisbane, Australia
(author)
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Ngo, Shyuan T.Centre for Clinical Research, University of Queensland, QLD, Brisbane, Australia; Australian Institute for Bioengineering and Nanotechnology, University of Queensland, QLD, Brisbane, Australia; Queensland Brain Institute, University of Queensland, QLD, Brisbane, Australia
(author)
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Steyn, Frederik J.Centre for Clinical Research, University of Queensland, QLD, Brisbane, Australia; School of Biomedical Sciences, University of Queensland, QLD, Brisbane, Australia
(author)
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Wallace, LeanneInstitute for Molecular Bioscience, University of Queensland, Brisbane, Australia
(author)
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Williams, Kelly L.Centre for Motor Neuron Disease Research, Macquarie University, NSW, Australia
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Neto, Miguel MitneUniversidade de São Paulo, São Paulo, Brazil
(author)
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Cauchi, Ruben J.Center for Molecular Medicine and Biobanking, Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, Msida, Malta
(author)
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Blair, Ian P.Centre for Motor Neuron Disease Research, Macquarie University, NSW, Australia
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Kiernan, Matthew C.Brain and Mind Centre, University of Sydney, NSW, Sydney, Australia; Department of Neurology, Royal Prince Alfred Hospital, NSW, Sydney, Australia
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Drory, VivianDepartment of Neurology, Tel-Aviv Sourasky Medical Centre, Tel-Aviv, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
(author)
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Povedano, MonicaFunctional Unit of Amyotrophic Lateral Sclerosis (UFELA), Service of Neurology, Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain
(author)
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de Carvalho, MamedeInstituto de Fisiologia, Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
(author)
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Pinto, SusanaInstituto de Fisiologia, Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
(author)
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Weber, MarkusNeuromuscular Diseases Unit, ALS Clinic, Kantonsspital St. Gallen, St. Gallen, Switzerland
(author)
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Rouleau, Guy A.Montréal Neurological Institute and Hospital, McGill University, QC, Montréal, Canada
(author)
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Silani, VincenzoDepartment of Neurology-Stroke Unit, Laboratory of Neuroscience, Istituto Auxologico Italiano IRCCS, Milan, Italy; Department of Pathophysiology and Transplantation, “Dino Ferrari” Center, Università degli Studi di Milano, Milan, Italy
(author)
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Landers, John E.Department of Neurology, University of Massachusetts, Medical School, MA, Worcester, United States
(author)
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Shaw, Christopher E.Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
(author)
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Andersen, Peter M.,1962-Umeå universitet,Neurovetenskaper(Swepub:umu)pean0001
(author)
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McRae, Allan F.Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia
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van Es, Michael A.Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, Netherlands
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Pasterkamp, R. JeroenDepartment of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, Netherlands
(author)
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Wray, Naomi R.Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia; Queensland Brain Institute, University of Queensland, QLD, Brisbane, Australia
(author)
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McLaughlin, Russell L.Complex Trait Genomics Laboratory, Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland
(author)
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Hardiman, OrlaAcademic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland
(author)
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Kenna, Kevin P.Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, Netherlands; Department of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, Netherlands
(author)
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Tsai, EllenTranslational Biology, Biogen, MA, Boston, United States
(author)
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Runz, HeikoTranslational Biology, Biogen, MA, Boston, United States
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Al-Chalabi, AmmarMaurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; King's College Hospital, Denmark Hill, London, United Kingdom
(author)
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van den Berg, Leonard H.Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, Netherlands
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Van Damme, PhilipKU Leuven, University of Leuven, Department of Neurosciences, Experimental Neurology and Leuven Brain Institute (LBI), Leuven, Belgium; VIB, Center for Brain and Disease Research, Leuven, Belgium; University Hospitals Leuven, Department of Neurology, Leuven, Belgium
(author)
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Mill, JonathanUniversity of Exeter Medical School, College of Medicine and Health, University of Exeter, Exeter, United Kingdom
(author)
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Veldink, Jan H.Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, Netherlands
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Heijmans, Bastiaan T.Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, Netherlands
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t Hoen, Peter A.C.Department of Human Genetics, Leiden University Medical Center, Leiden, Netherlands
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van Meurs, JoyceDepartment of Internal Medicine, ErasmusMC, Rotterdam, Netherlands
(author)
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Jansen, RickDepartment of Psychiatry, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, Netherlands
(author)
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Franke, LudeDepartment of Genetics, University of Groningen, University Medical Centre Groningen, Groningen, Netherlands
(author)
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Boomsma, Dorret I.Depart-ment of Biological Psychology, VU University Amsterdam, Neuroscience Campus Amsterdam, Amsterdam, Netherlands
(author)
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Pool, RenéDepart-ment of Biological Psychology, VU University Amsterdam, Neuroscience Campus Amsterdam, Amsterdam, Netherlands
(author)
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van Dongen, JennyDepart-ment of Biological Psychology, VU University Amsterdam, Neuroscience Campus Amsterdam, Amsterdam, Netherlands
(author)
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Hottenga, Joukje J.Depart-ment of Biological Psychology, VU University Amsterdam, Neuroscience Campus Amsterdam, Amsterdam, Netherlands
(author)
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van Greevenbroek, Marleen M.J.Department of Internal Medicine, School for Cardiovascular Diseases (CARIM), Maastricht University Medical Center, Maastricht, Netherlands
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Stehouwer, Coen D.A.Department of Internal Medicine, School for Cardiovascular Diseases (CARIM), Maastricht University Medical Center, Maastricht, Netherlands
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van der Kallen, Carla J.H.Department of Internal Medicine, School for Cardiovascular Diseases (CARIM), Maastricht University Medical Center, Maastricht, Netherlands
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Schalkwijk, Casper G.Department of Internal Medicine, School for Cardiovascular Diseases (CARIM), Maastricht University Medical Center, Maastricht, Netherlands
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Wijmenga, CiscaDepartment of Genetics, University of Groningen, University Medical Centre Groningen, Groningen, Netherlands
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Zhernakova, SashaDepartment of Genetics, University of Groningen, University Medical Centre Groningen, Groningen, Netherlands
(author)
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Tigchelaar, Ettje F.Department of Genetics, University of Groningen, University Medical Centre Groningen, Groningen, Netherlands
(author)
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Slagboom, P. ElineMolecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, Netherlands
(author)
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Beekman, MarianMolecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, Netherlands
(author)
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Deelen, JorisMolecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, Netherlands
(author)
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van Heemst, DianaDepartment of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, Netherlands
(author)
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van Duijn, Cornelia M.Department of Genetic Epidemiology, ErasmusMC, Rotterdam, Netherlands
(author)
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Hofman, Bert A.Department of Epidemiology, ErasmusMC, Rotterdam, Netherlands
(author)
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Isaacs, AaronDepartment of Genetic Epidemiology, ErasmusMC, Rotterdam, Netherlands
(author)
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Uitterlinden, André G.Department of Internal Medicine, ErasmusMC, Rotterdam, Netherlands
(author)
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Jhamai, P. MilaDepartment of Internal Medicine, ErasmusMC, Rotterdam, Netherlands
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Verbiest, MichaelDepartment of Internal Medicine, ErasmusMC, Rotterdam, Netherlands
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Suchiman, Eka H.D.Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, Netherlands
(author)
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Verkerk, MarijnDepartment of Internal Medicine, ErasmusMC, Rotterdam, Netherlands
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van der Breggen, RuudMolecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, Netherlands
(author)
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van Rooij, JeroenDepartment of Internal Medicine, ErasmusMC, Rotterdam, Netherlands
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Lakenberg, NicoMolecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, Netherlands
(author)
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Mei, HailiangSequence Analysis Support Core, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, Netherlands
(author)
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van Iterson, MaartenMolecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, Netherlands
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van Galen, MichielDepartment of Human Genetics, Leiden University Medical Center, Leiden, Netherlands
(author)
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Bot, JanSURFsara, Amsterdam, Netherlands
(author)
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van 'T Hof, PeterSequence Analysis Support Core, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, Netherlands
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Nooren, IreneSURFsara, Amsterdam, Netherlands
(author)
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Moed, MatthijsMolecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, Netherlands
(author)
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Vermaat, MartijnDepartment of Human Genetics, Leiden University Medical Center, Leiden, Netherlands
(author)
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Luijk, RenéMolecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, Netherlands
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Bonder, Marc JanDepartment of Genetics, University of Groningen, University Medical Centre Groningen, Groningen, Netherlands
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van Dijk, FreerkGenomics Coordination Center, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
(author)
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Arindrarto, WibowoSequence Analysis Support Core, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, Netherlands
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Kielbasa, Szymon M.Medical Statistics, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, Netherlands
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Swertz, Morris A.Genomics Coordination Center, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
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van Zwet, Erik W.Medical Statistics, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, Netherlands
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Bensimon, GilbertQueensland Brain Institute, University of Queensland, QLD, Brisbane, Australia; Département de Pharmacologie Clinique, Hôpital de la Pitié-Salpêtrière, UPMC Pharmacologie, AP-HP, Paris, France
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Smith, George DaveyMRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom; Population Health Science, Bristol Medical School, Bristol, Bristol, United Kingdom
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Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, NetherlandsUniversity of Exeter Medical School, College of Medicine and Health, University of Exeter, Exeter, United Kingdom
(creator_code:org_t)
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In:Science Translational Medicine: American Association for the Advancement of Science14:6331946-62341946-6242
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Hop, Paul J.
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Zwamborn, Ramona ...
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Hannon, Eilis
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Shireby, Gemma L ...
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Nabais, Marta F.
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Shaw, Pamela J.
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Canosa, Antonio
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Gotkine, Marc
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Salas, Teresa
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Mathers, Susan
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McCombe, Pamela ...
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Nicholson, Garth
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Rowe, Dominic B.
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de Carvalho, Mam ...
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Pinto, Susana
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Landers, John E.
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Andersen, Peter ...
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McRae, Allan F.
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van Es, Michael ...
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McLaughlin, Russ ...
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Hardiman, Orla
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Tsai, Ellen
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Runz, Heiko
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Van Damme, Phili ...
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Mill, Jonathan
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Veldink, Jan H.
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Heijmans, Bastia ...
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t Hoen, Peter A. ...
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van Dongen, Jenn ...
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Hottenga, Joukje ...
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van Greevenbroek ...
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van der Kallen, ...
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Tigchelaar, Ettj ...
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Deelen, Joris
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van Heemst, Dian ...
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van Duijn, Corne ...
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Hofman, Bert A.
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Isaacs, Aaron
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Uitterlinden, An ...
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Verbiest, Michae ...
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van der Breggen, ...
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van Rooij, Jeroe ...
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van 'T Hof, Pete ...
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Nooren, Irene
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