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. 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

Arvid Rongve  1   2 , Aree Witoelar  3   4 , Agustín Ruiz  5 , Lavinia Athanasiu  3   4 , Carla Abdelnour  5 , Jordi Clarimon  6   7 , Stefanie Heilmann-Heimbach  8   9 , Isabel Hernández  5 , Sonia Moreno-Grau  5 , Itziar de Rojas  5 , Estrella Morenas-Rodríguez  6   7 , Tormod Fladby  10   11 , Sigrid B Sando  12 , Geir Bråthen  13 , Frédéric Blanc  14   15 , Olivier Bousiges  16 , Afina W Lemstra  17   18 , Inger van Steenoven  17   18 , Elisabet Londos  19 , Ina S Almdahl  11   20 , Lene Pålhaugen  10   11 , Jon A Eriksen  3   4 , Srdjan Djurovic  21   22 , Eystein Stordal  23   24 , Ingvild Saltvedt  12   25 , Ingun D Ulstein  4   20 , Francesco Bettella  3 , Rahul S Desikan  26 , Ane-Victoria Idland  27   28   29 , Mathias Toft  4   30 , Lasse Pihlstrøm  30 , Jon Snaedal  31 , Lluís Tárraga  5 , Mercè Boada  5 , Alberto Lleó  6   7 , Hreinn Stefánsson  32 , Kári Stefánsson  32 , Alfredo Ramírez  33   34 , Dag Aarsland  35   36 , Ole A Andreassen  37   38
Affiliations

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

Arvid Rongve et al. Sci Rep. .

Erratum in

  • Author Correction: GBA and APOE ε4 associate with sporadic dementia with Lewy bodies in European genome wide association study.
    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, Andreassen OA. Rongve A, et al. Sci Rep. 2019 Oct 17;9(1):15168. doi: 10.1038/s41598-019-51827-0. Sci Rep. 2019. PMID: 31619746 Free PMC article.

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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Conflict of interest statement

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 Fladbym, Sigrid B. Sando, Geir Bråthen, Frédéric Blanc, Olivier Bousiges, Afina W. Lemstra, Inger van Steenoven, Elisabet Londos, Ina S. Almdahl, Lene 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 and Alfredo Ramírez declare no competing interests. Kári Stefánsson and Hreinn Stefánsson are employees of deCODE Genetics, Iceland. Ole A. Andreassen has received speaker’s honorarium from Lundbeck and has a pending patent for biostatistical genetic methodology. Dr Aarsland has received research support and/or honoraria from Astra-Zeneca, H. Lundbeck, Novartis Pharmaceuticals and GE Health, and served as paid consultant for H. Lundbeck, Eisai, Heptares, Safnoi, Mentis Cura. Dag Aarsland is a Royal Society Wolfson Research Merit Award Holder and would like to thank the Wolfson Foundation and the Royal Society for their support.

Figures

Figure 1
Figure 1
Manhattan plot of Stage 1 meta-analysis. Manhattan plot of meta-analysis of Cohorts 1 and 2 for genome-wide association with Dementia with Lewy Body (DLB). Genome-wide significant associations to DLB (threshold P < 5 × 10−8) are found in chromosomes 1 (ASH1L/GBA) and 19 (APOE), and a suggestive association to DLB at P < 1 × 10−6 is identified at chromosome 16 (ZFPM1). A comprehensive result of Stage 1 is presented in Supplementary Table 2.
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