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Sökning: onr:"swepub:oai:DiVA.org:oru-102658" > Whole-exome rare-va...

Whole-exome rare-variant analysis of Alzheimer's disease and related biomarker traits

Küçükali, Fahri (författare)
Complex Genetics of Alzheimer's Disease Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium
Neumann, Alexander (författare)
Complex Genetics of Alzheimer's Disease Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium
Van Dongen, Jasper (författare)
Complex Genetics of Alzheimer's Disease Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium
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De Pooter, Tim (författare)
Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Neuromics Support Facility, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium
Joris, Geert (författare)
Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Neuromics Support Facility, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium
De Rijk, Peter (författare)
Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Neuromics Support Facility, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium
Ohlei, Olena (författare)
Lübeck Interdisciplinary Platform for Genome Analytics (LIGA), University of Lübeck, Lübeck, Germany
Dobricic, Valerija (författare)
Lübeck Interdisciplinary Platform for Genome Analytics (LIGA), University of Lübeck, Lübeck, Germany
Bos, Isabelle (författare)
Netherlands Institute for Health Services Research, Utrecht, Netherlands
Vos, Stephanie J. B. (författare)
Alzheimer Centrum Limburg, Maastricht University, Maastricht, Netherlands
Engelborghs, Sebastiaan (författare)
Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Department of Neurology and Brussels Integrated Center for Brain and Memory (Bru-BRAIN), Universitair Ziekenhuis Brussel (UZ Brussel) and Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Brussels, Belgium
De Roeck, Ellen (författare)
Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium
Vandenberghe, Rik (författare)
University Hospital Leuven, Leuven, Belgium; Department of Neurosciences, Laboratory for Cognitive Neurology, KU Leuven, Leuven, Belgium
Gabel, Silvy (författare)
University Hospital Leuven, Leuven, Belgium; Department of Neurosciences, Laboratory for Cognitive Neurology, KU Leuven, Leuven, Belgium
Meersmans, Karen (författare)
University Hospital Leuven, Leuven, Belgium; Department of Neurosciences, Laboratory for Cognitive Neurology, KU Leuven, Leuven, Belgium
Tsolaki, Magda (författare)
1st Department of Neurology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Makedonia, Thessaloniki, Greece
Verhey, Frans (författare)
Alzheimer Centrum Limburg, Maastricht University, Maastricht, Netherlands; Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, Netherlands; School for Mental Health and Neuroscience, Maastricht University, Maastricht, Netherlands
Martinez-Lage, Pablo (författare)
Center for Research and Advanced Therapies, CITA-Alzheimer Foundation, San Sebastian, Spain
Tainta, Mikel (författare)
Center for Research and Advanced Therapies, CITA-Alzheimer Foundation, San Sebastian, Spain
Frisoni, Giovanni (författare)
Department of Psychiatry, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland; RCCS Instituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy
Blin, Oliver (författare)
Clinical Pharmacology & Pharmacovigilance Department, Marseille University Hospital, Marseille, France
Richardson, Jill C. (författare)
Neurosciences Therapeutic Area, GlaxoSmithKline R&D, Stevanage, United Kingdom
Bordet, Régis (författare)
Neuroscience & Cognition, CHU de Lille, University of Lille, Inserm, France
Scheltens, Philip (författare)
Alzheimer Center and Department of Neurology, VU University Medical Center, Amsterdam, Netherlands; Alzheimer's Disease Neuroimaging Initiative (ADNI)
Popp, Julius (författare)
Department of Geriatric Psychiatry, University Hospital of Psychiatry Zürich, Zürich, Switzerland; Department of Psychiatry, Old Age Psychiatry, University Hospital of Lausanne, Lausanne, Switzerland
Peyratout, Gwendoline (författare)
Department of Psychiatry, University Hospital of Lausanne, Lausanne, Switzerland
Johannsen, Peter (författare)
Clinical Drug Development, Novo Nordisk, Copenhagen, Denmark
Frölich, Lutz (författare)
Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
Freund-Levi, Yvonne, 1956- (författare)
Karolinska Institutet,Örebro universitet,Institutionen för medicinska vetenskaper,Departments of Geriatrics, University Hospital Örebro, Örebro, Sweden; Department of Clinical Science and Education, Södertälje Hospital, Södersjukhuset Karolinska Institutet, Stockholm, Sweden
Streffer, Johannes (författare)
Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium
Lovestone, Simon (författare)
Department of Psychiatry, University of Oxford, Oxford, United Kingdom; Janssen Medical Ltd, High Wycombe, United Kingdom
Legido-Quigley, Cristina (författare)
Steno Diabetes Center, Copenhagen, Denmark; Institute of Pharmaceutical Sciences, King's College London, London, United Kingdom
Kate, Mara Ten (författare)
Alzheimer Center and Department of Neurology, VU University Medical Center, Amsterdam, Netherlands; Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, Netherlands
Barkhof, Frederik (författare)
Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, Netherlands; Queen Square Institute of Neurology and Centre for Medical Image Computing, University College London, London, United Kingdom
Zetterberg, Henrik, 1973 (författare)
Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Bertram, Lars (författare)
Lübeck Interdisciplinary Platform for Genome Analytics (LIGA), University of Lübeck, Lübeck, Germany; Centre for Lifespan Changes in Brain and Cognition, University of Oslo, Oslo, Norway
Strazisar, Mojca (författare)
Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Neuromics Support Facility, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium
Visser, Pieter Jelle (författare)
Alzheimer Centrum Limburg, Maastricht University, Maastricht, Netherlands; Alzheimer Center and Department of Neurology, VU University Medical Center, Amsterdam, Netherlands
Van Broeckhoven, Christine (författare)
Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Neurodegenerative Brain Diseases Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium
Sleegers, Kristel (författare)
Complex Genetics of Alzheimer's Disease Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium
EMIF-AD Study Group, - (bidragsgivare)
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 (creator_code:org_t)
2022-12-04
2023
Engelska.
Ingår i: Alzheimer's & Dementia. - : John Wiley & Sons. - 1552-5260 .- 1552-5279. ; 19:6, s. 2317-2331
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • INTRODUCTION: Despite increasing evidence of a role of rare genetic variation in the risk of Alzheimer's disease (AD), limited attention has been paid to its contribution to AD-related biomarker traits indicative of AD-relevant pathophysiological processes.METHODS: We performed whole-exome gene-based rare-variant association studies (RVASs) of 17 AD-related traits on whole-exome sequencing (WES) data generated in the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery (EMIF-AD MBD) study (n = 450) and whole-genome sequencing (WGS) data from ADNI (n = 808).RESULTS: Mutation screening revealed a novel probably pathogenic mutation (PSEN1 p.Leu232Phe). Gene-based RVAS revealed the exome-wide significant contribution of rare coding variation in RBKS and OR7A10 to cognitive performance and protection against left hippocampal atrophy, respectively.DISCUSSION: The identification of these novel gene-trait associations offers new perspectives into the role of rare coding variation in the distinct pathophysiological processes culminating in AD, which may lead to identification of novel therapeutic and diagnostic targets.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Nyckelord

Alzheimer's disease
biomarkers
endophenotypes
rare coding variants
whole-exome sequencing
Alzheimer's disease
biomarkers
endophenotypes
rare coding variants
whole-exome sequencing

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