1. GBA and APOE ε4 associate with sporadic dementia with Lewy bodies in European genome wide association study.
- Author
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Rongve A, Witoelar A, Ruiz A, Athanasiu L, Abdelnour C, Clarimon J, Heilmann-Heimbach S, Hernández I, Moreno-Grau S, de Rojas I, Morenas-Rodríguez E, Fladby T, Sando SB, Bråthen G, Blanc F, Bousiges O, Lemstra AW, van Steenoven I, Londos E, Almdahl IS, Pålhaugen L, Eriksen JA, Djurovic S, Stordal E, Saltvedt I, Ulstein ID, Bettella F, Desikan RS, Idland AV, Toft M, Pihlstrøm L, Snaedal J, Tárraga L, Boada M, Lleó A, Stefánsson H, Stefánsson K, Ramírez A, Aarsland D, and Andreassen OA
- Subjects
- Case-Control Studies, Europe, Genetic Loci, Genetic Predisposition to Disease, Humans, Iceland, Norway, Nuclear Proteins genetics, Transcription Factors genetics, Apolipoproteins E genetics, Genome-Wide Association Study methods, Glucosylceramidase genetics, Lewy Body Disease genetics, Polymorphism, Single Nucleotide
- 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.- Published
- 2019
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