期刊
SCIENTIFIC REPORTS
卷 9, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-019-43458-2
关键词
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资金
- Research Council of Norway
- Norwegian Regional Health Authorities
- Norwegian Health Association
- APGeM [237250/EU/JPND]
- ISCIII(Instituto de Salud Carlos III)-Subdireccion General de Evaluacion
- Fondo Europeo de Desarrollo Regional (FEDER-Una manera de Hacer Europa)
- Fundacion bancaria La Caixa, Grifols SA, Fundacio ACE
- [PI13/02434]
- [PI16/01861]
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 epsilon 4 (Chr19) loci were associated with DLB surpassing the genome-wide significance threshold (p < 5 x 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 x 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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