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

• Published in: Scientific Reports
• Main Authors: Rongve, Arvid, Witoelar, Aree, Ruiz, Agustín, Athanasiu, Lavinia, Abdelnour, Carla, Clarimon, Jordi, Heilmann-Heimbach, Stefanie, Hernández, Isabel, Moreno-Grau, Sonia, de Rojas, Itziar, Morenas-Rodríguez, Estrella, Fladby, Tormod, Sando, Sigrid B., Bråthen, Geir, Blanc, Frederic, Bousiges, Olivier, Lemstra, Afina W., van Steenoven, Inger, Londos, Elisabet, Almdahl, Ina S., Pålhaugen, Lene, Eriksen, Jon A., Djurovic, Srdjan, Stordal, Eystein, Saltvedt, Ingvild, Ulstein, Ingun D., Bettella, Francesco, Desikan, Rahul S., Idland, Ane-Victoria, Toft, Mathias, Pihlstrøm, Lasse, Snaedal, Jon, Tárraga, Lluís, Boada, Mercè, Lleó, Alberto, Stefánsson, Hreinn, Stefánsson, Kári, Ramírez, Alfredo, Aarsland, Dag, Andreassen, Ole A.
• Other Authors: Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de neurosciences cognitives et adaptatives (LNCA), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)
• Format: Article in Journal/Newspaper
• Language: English
• Published: HAL CCSD 2019
• Subjects: [SCCO.NEUR]Cognitive science/Neuroscience; Iceland
• Online Access: https://hal.archives-ouvertes.fr/hal-02935002; https://hal.archives-ouvertes.fr/hal-02935002/document; https://hal.archives-ouvertes.fr/hal-02935002/file/islandora_83285.pdf; https://doi.org/10.1038/s41598-019-43458-2

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.