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Insights into TREM2 biology by network analysis of human brain gene expression data

Forabosco, Paola and Ramasamy, Adaikalavan and Trabzuni, Daniah and Walker, Robert and Smith, Colin and Bras, Jose and Levine, Adam P. and Hardy, John and Pocock, Jennifer M. and Guerreiro, Rita and Weale, Michael E. and Ryten, Mina (2013) Insights into TREM2 biology by network analysis of human brain gene expression data. Neurobiology of Aging, Vol. 34 (12), p. 2699-2714. ISSN 0197-4580. Article.

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DOI: 10.1016/j.neurobiolaging.2013.05.001

Abstract

Rare variants in TREM2 cause susceptibility to late-onset Alzheimer's disease. Here we use microarray-based expression data generated from 101 neuropathologically normal individuals and covering 10 brain regions, including the hippocampus, to understand TREM2 biology in human brain. Using network analysis, we detect a highly preserved TREM2-containing module in human brain, show that it relates to microglia, and demonstrate that TREM2 is a hub gene in 5 brain regions, including the hippocampus, suggesting that it can drive module function. Using enrichment analysis we show significant overrepresentation of genes implicated in the adaptive and innate immune system. Inspection of genes with the highest connectivity to TREM2 suggests that it plays a key role in mediating changes in the microglial cytoskeleton necessary not only for phagocytosis, but also migration. Most importantly, we show that the TREM2-containing module is significantly enriched for genes genetically implicated in Alzheimer's disease, multiple sclerosis, and motor neuron disease, implying that these diseases share common pathways centered on microglia and that among the genes identified are possible new disease-relevant genes.

Item Type:Article
ID Code:9223
Status:Published
Refereed:Yes
Uncontrolled Keywords:TREM2, weighted gene co-expression network analysis, Alzheimer's disease, post-mortem human brain, microglia, immune system
Subjects:Area 06 - Scienze mediche > MED/03 Genetica medica
Divisions:002 Altri enti e centri di ricerca del Nord Sardegna > CNR-Consiglio Nazionale delle Ricerche > Istituto di genetica delle popolazioni, Alghero
Publisher:Elsevier
ISSN:0197-4580
Deposited On:01 Oct 2013 10:49

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