Systems biology approach to late-onset Alzheimer's disease genome-wide association study identifies novel candidate genes validated using brain expression data and Caenorhabditis elegans experiments.
Systems biology approach to late-onset Alzheimer's disease genome-wide association study identifies novel candidate genes validated using brain expression data and Caenorhabditis elegans experiments.
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系统生物学方法对迟到的阿尔茨海默氏病基因组基因组关联研究确定了使用脑表达数据和秀丽隐杆线虫实验验证的新型候选基因。
DOI：
10.1016/j.jalz.2017.01.016
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发表时间：
2017-10
期刊：
影响因子：
--
通讯作者：
Crane PK
中科院分区：
文献类型：
--
作者：
Mukherjee S;Russell JC;Carr DT;Burgess JD;Allen M;Serie DJ;Boehme KL;Kauwe JSK;Naj AC;Fardo DW;Dickson DW;Montine TJ;Ertekin-Taner N;Kaeberlein MR;Crane PK
We sought to determine whether a systems biology approach may identify novel late-onset Alzheimer’s disease (LOAD) loci. We performed gene-wide association analyses and integrated results with human protein-protein interaction data using network analyses. We performed functional validation on novel genes using a transgenic Caenorhabditis elegans Aβ proteotoxicity model and evaluated novel genes using brain expression data from people with LOAD and other neurodegenerative conditions. We identified 13 novel candidate LOAD genes outside chromosome 19. Of those, RNA interference knockdowns of the C. elegans orthologs of UBC, NDUFS3, EGR1, and ATP5H were associated with Aβ toxicity, and NDUFS3, SLC25A11, ATP5H, and APP were differentially expressed in the temporal cortex. Network analyses identified novel LOAD candidate genes. We demonstrated a functional role for four of these in a C. elegans model and found enrichment of differentially expressed genes in the temporal cortex.
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影响因子：
4.8
作者：
Atkin G;Paulson H
通讯作者：
Paulson H
影响因子：
64.5
作者：
Duce JA;Tsatsanis A;Cater MA;James SA;Robb E;Wikhe K;Leong SL;Perez K;Johanssen T;Greenough MA;Cho HH;Galatis D;Moir RD;Masters CL;McLean C;Tanzi RE;Cappai R;Barnham KJ;Ciccotosto GD;Rogers JT;Bush AI
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Tienari, Pentti J.
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9.8
作者：
Liu, Jimmy Z.;Mcrae, Allan F.;Macgregor, Stuart
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Macgregor, Stuart
影响因子：
3.7
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Akula N;Baranova A;Seto D;Solka J;Nalls MA;Singleton A;Ferrucci L;Tanaka T;Bandinelli S;Cho YS;Kim YJ;Lee JY;Han BG;Bipolar Disorder Genome Study (BiGS) Consortium;Wellcome Trust Case-Control Consortium;McMahon FJ
通讯作者：
McMahon FJ