GBA and APOE ε4 associate with sporadic dementia with Lewy bodies in European genome wide association study
Rongve, A. (The University of Bergen)
Witoelar, Aree (University of Oslo. Institute of Clinical Medicine)
Ruiz, Agustín (Fundació ACE)
Athanasiu, Lavinia (University of Oslo)
Abdelnour, Carla (Fundació ACE)
Clarimón, Jordi (Institut d'Investigació Biomèdica Sant Pau)
Heilmann-Heimbach, Stefanie (University of Bonn)
Hernández, Isabel (Fundació ACE)
Moreno-Grau, Sonia (Fundació ACE)
De Rojas, Itziar (Fundació ACE)
Morenas-Rodríguez, Estrella (Institut d'Investigació Biomèdica Sant Pau)
Fladby, Tormod (University of Oslo)
Sando, Sigrid B. (Norwegian University of Science and Technology)
Bråthen, Geir (St Olav's University Hospital)
Blanc, Frédéric (University of Strasbourg)
Bousiges, Olivier (University Hospital of Strasbourg)
Lemstra, Afina W. (Amsterdam UMC. University Medical Center)
van Steenoven, Inger (Amsterdam UMC. University Medical Center)
Londos, Elisabet (Skåne University Hospital (Suècia))
Almdahl, Ina S. (Oslo University Hospital (Oslo, Noruega))
Pålhaugen, Lene (University of Oslo)
Eriksen, Jon A. (University of Oslo)
Djurovic, Srdjan (University of Bergen)
Stordal, Eystein (Norwegian University of Science and Technology)
Saltvedt, Ingvild (St Olav's University Hospital)
Ulstein, Ingun D. (Oslo University Hospital (Oslo, Noruega))
Bettella, Francesco (Oslo University Hospital (Oslo, Noruega))
Desikan, Rahul S. (Neurology and Pediatrics, UCSF.)
Idland, Ane-Victoria (University of Oslo. Institute of Basic Medical Sciences)
Toft, Mathias (Oslo University Hospital (Oslo, Noruega))
Pihlstrøm, Lasse (Oslo University Hospital (Oslo, Noruega))
Snaedal, Jon (Landspitali University Hospital (Reykjavík, Islàndia))
Tárraga, Lluís (Fundació ACE)
Boada, Mercè (Fundació ACE)
Lleó, Alberto (Institut d'Investigació Biomèdica Sant Pau)
Stefánsson, Hreinn (deCODE Genetics (Reykjavík, Islàndia))
Stefánsson, Kári (deCODE Genetics (Reykjavík, Islàndia))
Ramirez, Alfredo (University of Bonn)
Aarsland, Dag (Stavanger University Hospital)
Andreassen, Ole A. (University of Oslo)
Universitat Autònoma de Barcelona

Date:	2019
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). 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. 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.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Apolipoproteins ; Case-Control Studies ; Europe ; Genetic Loci ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Glucosylceramidase ; Humans ; Iceland ; Lewy Body Disease ; Norway ; Nuclear Proteins ; Polymorphism, Single Nucleotide ; Transcription Factors
Published in:	Scientific reports, Vol. 9 Núm. 1 (january 2019) , p. 7013, ISSN 2045-2322

Erratum: https://ddd.uab.cat/record/253362
DOI: 10.1038/s41598-019-43458-2
PMID: 31065058

8 p, 1.2 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles