GBA and APOE ε4 associate with sporadic dementia with Lewy bodies in European genome wide association study.
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de Rojas, Itziar
Sando, Sigrid B
Lemstra, Afina W
van Steenoven, Inger
Almdahl, Ina S
Eriksen, Jon A
Ulstein, Ingun D
Desikan, Rahul S
Andreassen, Ole A
MetadataShow full item record
CitationGBA and APOE ε4 associate with sporadic dementia with Lewy bodies in European genome wide association study. 2019, 9(1):7013 Sci Rep
AbstractDementia 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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