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

Arvid Rongve, Aree Witoelar, Agustín Ruiz, Lavinia Athanasiu, Carla Abdelnour, Jordi Clarimon, Stefanie Heilmann-Heimbach, Isabel Hernández, Sonia Moreno-Grau, Itziar de Rojas, Estrella Morenas-Rodríguez, Tormod Fladby, Sigrid B. Sando, Geir Bråthen, Frédéric Blanc, Olivier Bousiges, Afina W. Lemstra, Inger van Steenoven, Elisabet Londos, Ina S. AlmdahlLene Pålhaugen, Jon A. Eriksen, Srdjan Djurovic, Eystein Stordal, Ingvild Saltvedt, Ingun D. Ulstein, Francesco Bettella, Rahul S. Desikan, Ane-Victoria Idland, Mathias Toft, Lasse Pihlstrøm, Jon Snaedal, Lluís Tárraga, Mercè Boada, Alberto Lleó, Hreinn Stefánsson, K. ri Stefánsson, Alfredo Ramírez, Dag Aarsland, Ole A. Andreassen

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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.
Original languageEnglish
Article number7013
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - 2019

Cite this

Rongve, A., Witoelar, A., Ruiz, A., Athanasiu, L., Abdelnour, C., Clarimon, J., ... Andreassen, O. A. (2019). GBA and APOE ε4 associate with sporadic dementia with Lewy bodies in European genome wide association study. Scientific Reports, 9(1), [7013]. https://doi.org/10.1038/s41598-019-43458-2