Interactions between genes involved in physiological dysregulation and axon guidance: role in Alzheimer's disease.
Interactions between genes involved in physiological dysregulation and axon guidance: role in Alzheimer's disease.
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DOI：
10.3389/fgene.2023.1236509
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发表时间：
2023
影响因子：
3.7
通讯作者：
Yashin, Anatoliy I.
中科院分区：
文献类型：
--
作者：
Arbeev, Konstantin G.;Ukraintseva, Svetlana;Bagley, Olivia;Duan, Hongzhe;Wu, Deqing;Akushevich, Igor;Stallard, Eric;Kulminski, Alexander;Christensen, Kaare;Feitosa, Mary F.;O'Connell, Jeffrey R.;Parker, Daniel;Whitson, Heather;Yashin, Anatoliy I.
关键词：
生理过程失调可能导致阿尔茨海默病（AD）的发展。我们之前发现，在衰老的身体中，生理失调（PD）水平的增加与对主要疾病的恢复力和健壮性下降有关。此外，我们的全基因组关联研究发现，与年龄相关的PD增加相关的基因经常代表与轴突引导和突触功能相关的途径，这些途径反过来又与AD和相关特征（如淀粉样蛋白、tau蛋白、神经变性）相关。在这里，我们验证了PD和轴突引导/突触功能相关基因可能共同影响AD发病的假设。我们在长寿家族研究中评估了这些基因中snp相互作用对阿尔茨海默病发病的影响，并试图复制健康与退休研究中的发现。我们发现，在两个数据集中，UNC5C和CNTN6、PLXNA4和EPHB2基因的snp之间存在显著的相互作用，影响AD的发病。与个体snp的相关性无统计学意义。因此，我们的研究结果支持了遗传相互作用在AD异质性中的主要作用，并表明PD和轴突引导/突触功能（对维持复杂神经网络至关重要）相关基因对AD发展的共同贡献。
Dysregulation of physiological processes may contribute to Alzheimer’s disease (AD) development. We previously found that an increase in the level of physiological dysregulation (PD) in the aging body is associated with declining resilience and robustness to major diseases. Also, our genome-wide association study found that genes associated with the age-related increase in PD frequently represented pathways implicated in axon guidance and synaptic function, which in turn were linked to AD and related traits (e.g., amyloid, tau, neurodegeneration) in the literature. Here, we tested the hypothesis that genes involved in PD and axon guidance/synapse function may jointly influence onset of AD. We assessed the impact of interactions between SNPs in such genes on AD onset in the Long Life Family Study and sought to replicate the findings in the Health and Retirement Study. We found significant interactions between SNPs in the UNC5C and CNTN6, and PLXNA4 and EPHB2 genes that influenced AD onset in both datasets. Associations with individual SNPs were not statistically significant. Our findings, thus, support a major role of genetic interactions in the heterogeneity of AD and suggest the joint contribution of genes involved in PD and axon guidance/synapse function (essential for the maintenance of complex neural networks) to AD development.
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影响因子：
3
作者：
Liu Z;Thakar A;Santoro SW;Pratt KG
通讯作者：
Pratt KG
影响因子：
7.8
作者：
Dansereau, Gabriel;Wey, Tina W.;Cohen, Alan A.
通讯作者：
Cohen, Alan A.
DOI：
10.1002/ajmg.b.32530
发表时间：
2017-06
期刊：
American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
影响因子：
--
作者：
Jia P;Zhao Z;Hulgan T;Bush WS;Samuels DC;Bloss CS;Heaton RK;Ellis RJ;Schork N;Marra CM;Collier AC;Clifford DB;Gelman BB;Sacktor N;Morgello S;Simpson DM;McCutchan JA;Barnholtz-Sloan JS;Franklin DR;Rosario D;Letendre SL;Grant I;Kallianpur AR;CHARTER Study Group
通讯作者：
CHARTER Study Group
影响因子：
2.1
作者：
Conomos MP;Miller MB;Thornton TA
通讯作者：
Thornton TA
影响因子：
4.8
作者：
Fagiani F;Lanni C;Racchi M;Govoni S
通讯作者：
Govoni S