Background:Both INPP5D and INPP5F are members of INPP5 family. INPP5F rs117896735 variant was associated with Parkinson’s disease (PD) risk, and INPP5D was an Alzheimer’s disease (AD) risk gene. However, it remains unclear about the roles of INPP5F rs117896735 variant in AD. Objective:We aim to investigate the roles of rs117896735 in AD. Methods:First, we conducted a candidate variant study to evaluate the association of rs117896735 variant with AD risk using the large-scale AD GWAS dataset. Second, we conducted a gene expression analysis of INPP5F to investigate the expression difference of INPP5F in different human tissues using two large-scale gene expression datasets. Third, we conducted an expression quantitative trait loci analysis to evaluate whether rs117896735 variant regulate the expression of INPP5F. Fourth, we explore the potentially differential expression of INPP5F in AD and control using multiple AD-control gene expression datasets in human brain tissues and whole blood. Results:We found that 1) rs117896735 A allele was associated with the increased risk of AD with OR = 1.15, 95% CI 1.005–1.315, p = 0.042; 2) rs117896735 A allele could increase INPP5F expression in multiple human tissues; 3) INPP5F showed different expression in different human tissues, especially in brain tissues; 4) INPP5F showed significant expression dysregulation in AD compared with controls in human brain tissues. Conclusion:Conclusion: We demonstrate that PD rs117896735 variant could regulate INPP5F expression in brain tissues and increase the risk of AD. These finding may provide important information about the role of rs117896735 in AD.

中文翻译：

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帕金森病 rs117896735 变体调节脑组织中 INPP5F 的表达并增加阿尔茨海默病的风险

背景：INPP5D和INPP5F都是INPP5家族的成员。INPP5F rs117896735 变异与帕金森病 (PD) 风险相关，INPP5D 是阿尔茨海默病 (AD) 风险基因。然而，目前尚不清楚 INPP5F rs117896735 变体在 AD 中的作用。目的：我们旨在研究 rs117896735 在 AD 中的作用。方法：首先，我们进行了一项候选变异研究，以使用大规模 AD GWAS 数据集评估 rs117896735 变异与 AD 风险的关联。其次，我们对 INPP5F 进行了基因表达分析，以使用两个大规模基因表达数据集研究 INPP5F 在不同人体组织中的表达差异。第三，我们进行了表达数量性状基因座分析，以评估 rs117896735 变异是否调节 INPP5F 的表达。第四，我们使用人脑组织和全血中的多个 AD 控制基因表达数据集探索 INPP5F 在 AD 和控制中的潜在差异表达。结果：我们发现 1) rs117896735 A 等位基因与 AD 风险增加相关，OR = 1.15，95% CI 1.005–1.315，p = 0.042；2) rs117896735等位基因可以增加多种人体组织中INPP5F的表达；3) INPP5F在不同的人体组织中表现出不同的表达，尤其是在脑组织中；4) 与人脑组织中的对照相比，INPP5F 在 AD 中表现出显着的表达失调。结论：结论：我们证明了 PD rs117896735 变异可以调节脑组织中 INPP5F 的表达并增加 AD 的风险。这些发现可能提供有关 rs117896735 在 AD 中的作用的重要信息。