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Sci Rep. 2019 May 7;9(1):7013. doi: 10.1038/s41598-019-43458-2.

GBA and APOE ε4 associate with sporadic dementia with Lewy bodies in European genome wide association study.

Author information

1
Haugesund Hospital, Helse Fonna, Department of Research and Innovation, Haugesund, Norway. arvid.rongve@helse-fonna.no.
2
The University of Bergen, Department of Clinical Medicine (K1), Bergen, Norway. arvid.rongve@helse-fonna.no.
3
NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
4
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
5
Memory Clinic and Research Center of Fundació ACE, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya (UIC), Barcelona, Spain.
6
Department of Neurology, IIB Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
7
Center for Networker Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid and Barcelona, Spain.
8
Institute of Human Genetics, University of Bonn, Bonn, Germany.
9
Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
10
Department of Neurology, Akershus University Hospital, Lørenskog, Norway.
11
University of Oslo, AHUS Campus, Oslo, Norway.
12
Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway.
13
Department of Neurology, St Olav's Hospital, Trondheim, Norway.
14
University Hospital of Strasbourg, CMRR (Memory Resources and Research Centre), Geriatrics Department, Strasbourg, France.
15
University of Strasbourg and CNRS, ICube laboratory and FMTS, team IMIS/Neurocrypto, Strasbourg, France.
16
University Hospital of Strasbourg, CMRR (Memory Resources and Research Centre), Laboratory of Biochemistry and Molecular Biology, Strasbourg, France.
17
University of Strasbourg and CNRS, Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), UMR7364, 67000, Strasbourg, France.
18
Alzheimercenter & Department of Neurology VU University Medical Center, Amsterdam, the Netherlands.
19
Lund University, Skane University Hospital, Institute of Clinical Sciences, Malmö, Sweden.
20
Department of Geriatric Psychiatry, Oslo University Hospital, Oslo, Norway.
21
Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
22
NORMENT, KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen, Norway.
23
Department of Psychiatry, Namsos Hospital, Namsos, Norway.
24
Department of Mental Health, Norwegian University of Science and Technology, Trondheim, Norway.
25
Department of Geriatrics, St. Olav's Hospital, Trondheim, Norway.
26
Departments of Radiology and Biomedical Imaging, Neurology and Pediatrics, UCSF, San Francisco, USA.
27
Oslo Delirium Research Group, Department of Geriatric Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
28
Research Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway.
29
Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
30
Department of Neurology, Oslo University Hospital, Oslo, Norway.
31
Landspitali University Hospital, Reykjavik, Iceland.
32
DeCODE genetics, Reykjavik, Iceland.
33
Division for Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Medical Faculty, University of Cologne, 50924, Cologne, Germany.
34
Department for Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn, 53127, Bonn, Germany.
35
Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. daarsland@gmail.com.
36
Center for Age-Related Diseases, Stavanger University Hospital, Stavanger, Norway. daarsland@gmail.com.
37
NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway. ole.andreassen@medisin.uio.no.
38
Institute of Clinical Medicine, University of Oslo, Oslo, Norway. ole.andreassen@medisin.uio.no.

Abstract

Dementia with Lewy Bodies (DLB) is a common neurodegenerative disorder with poor prognosis and mainly unknown pathophysiology. Heritability estimates exceed 30% but few genetic risk variants have been identified. Here we investigated common genetic variants associated with DLB in a large European multisite sample. We performed a genome wide association study in Norwegian and European cohorts of 720 DLB cases and 6490 controls and included 19 top-associated single-nucleotide polymorphisms in an additional cohort of 108 DLB cases and 75545 controls from Iceland. Overall the study included 828 DLB cases and 82035 controls. Variants in the ASH1L/GBA (Chr1q22) and APOE ε4 (Chr19) loci were associated with DLB surpassing the genome-wide significance threshold (p < 5 × 10-8). One additional genetic locus previously linked to psychosis in Alzheimer's disease, ZFPM1 (Chr16q24.2), showed suggestive association with DLB at p-value < 1 × 10-6. We report two susceptibility loci for DLB at genome-wide significance, providing insight into etiological factors. These findings highlight the complex relationship between the genetic architecture of DLB and other neurodegenerative disorders.

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