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

Rongve, Arvid; Witoelar, Aree; Ruiz, Agustín; Athanasiu, Lavinia; Abdelnour, Carla; Clarimon, Jordi; Heilmann-Heimbach, Stefanie; Hernández, Isabel; Moreno-Grau, Sonia and de Rojas, Itziar, et al. (2019) In Scientific Reports 9(1).
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)... (More)


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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Scientific Reports
volume
9
issue
1
publisher
Nature Publishing Group
external identifiers
  • scopus:85065429787
ISSN
2045-2322
DOI
10.1038/s41598-019-43458-2
language
English
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yes
id
63872b5d-9c7d-491a-bbb6-c147d9a4de44
date added to LUP
2019-05-22 08:38:17
date last changed
2019-06-11 04:05:31
@article{63872b5d-9c7d-491a-bbb6-c147d9a4de44,
  abstract     = {<p><br>
                                                         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 &lt; 5 × 10                             <br>
                            <sup>−8</sup><br>
                                                         ). One additional genetic locus previously linked to psychosis in Alzheimer’s disease, ZFPM1 (Chr16q24.2), showed suggestive association with DLB at p-value &lt; 1 × 10                             <br>
                            <sup>−6</sup><br>
                                                         . 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.                         <br>
                        </p>},
  articleno    = {7013},
  author       = {Rongve, Arvid and Witoelar, Aree and Ruiz, Agustín and Athanasiu, Lavinia and Abdelnour, Carla and Clarimon, Jordi and Heilmann-Heimbach, Stefanie and Hernández, Isabel and Moreno-Grau, Sonia and de Rojas, Itziar and Morenas-Rodríguez, Estrella and Fladby, Tormod and Sando, Sigrid B. and Bråthen, Geir and Blanc, Frédéric and Bousiges, Olivier and Lemstra, Afina W. and van Steenoven, Inger and Londos, Elisabet and Almdahl, Ina S. and Pålhaugen, Lene and Eriksen, Jon A. and Djurovic, Srdjan and Stordal, Eystein and Saltvedt, Ingvild and Ulstein, Ingun D. and Bettella, Francesco and Desikan, Rahul S. and Idland, Ane Victoria and Toft, Mathias and Pihlstrøm, Lasse and Snaedal, Jon and Tárraga, Lluís and Boada, Mercè and Lleó, Alberto and Stefánsson, Hreinn and Stefánsson, Kári and Ramírez, Alfredo and Aarsland, Dag and Andreassen, Ole A.},
  issn         = {2045-2322},
  language     = {eng},
  month        = {05},
  number       = {1},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {GBA and APOE ε4 associate with sporadic dementia with Lewy bodies in European genome wide association study},
  url          = {http://dx.doi.org/10.1038/s41598-019-43458-2},
  volume       = {9},
  year         = {2019},
}