GBA and APOE ε4 associate with sporadic dementia with Lewy bodies in European genome wide association study
GBA and APOE ε4 associate with sporadic dementia with Lewy bodies in European genome wide association study
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DOI：
10.1038/s41598-019-43458-2
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发表时间：
2019-05-07
影响因子：
4.6
通讯作者：
Andreassen, Ole A.
中科院分区：
文献类型：
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作者：
Rongve, Arvid;Witoelar, Aree;Andreassen, Ole A.
路易体痴呆（DLB）是一种常见的神经退行性疾病，预后较差，病理生理机制主要未知。遗传率估计超过30%，但很少发现有遗传风险的变异。在这里，我们研究了一个大型欧洲多地点样本中与DLB相关的常见遗传变异。我们对挪威和欧洲的720例DLB病例和6490例对照进行了全基因组关联研究，并在冰岛的108例DLB病例和75545例对照中发现了19个顶部相关的单核苷酸多态性。总的来说，研究包括828例DLB病例和82035例对照。ASH1L/GBA （Chr1q22）和APOE epsilon 4 （Chr19）位点的变异与DLB相关，超过全基因组显著阈值（p < 5 × 10(-8)）。另一个先前与阿尔茨海默病精神病相关的基因位点ZFPM1 （Chr16q24.2）显示与DLB有关联，p值< 1 × 10（-6）。我们报告了两个具有全基因组意义的DLB易感位点，为病因提供了见解。这些发现强调了DLB遗传结构与其他神经退行性疾病之间的复杂关系。
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.