Bonham, LW;
Steele, NZR;
Karch, CM;
Manzoni, C;
Geier, EG;
Wen, N;
Ofori-Kuragu, A;
... International FTD-Genomics Consortium (IFGC); + view all
(2018)
Protein network analysis reveals selectively vulnerable regions and biological processes in FTD.
Neurology Genetics
, 4
(5)
, Article e266. 10.1212/NXG.0000000000000266.
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Abstract
Objective: The neuroanatomical profile of behavioral variant frontotemporal dementia (bvFTD) suggests a common biological etiology of disease despite disparate pathologic causes; we investigated the genetic underpinnings of this selective regional vulnerability to identify new risk factors for bvFTD. Methods: We used recently developed analytical techniques designed to address the limitations of genome-wide association studies to generate a protein interaction network of 63 bvFTD risk genes. We characterized this network using gene expression data from healthy and diseased human brain tissue, evaluating regional network expression patterns across the lifespan as well as the cell types and biological processes most affected in bvFTD. Results: We found that bvFTD network genes show enriched expression across the human lifespan in vulnerable neuronal populations, are implicated in cell signaling, cell cycle, immune function, and development, and are differentially expressed in pathologically confirmed frontotemporal lobar degeneration cases. Five of the genes highlighted by our differential expression analyses, BAIAP2, ERBB3, POU2F2, SMARCA2, and CDC37, appear to be novel bvFTD risk loci. Conclusions: Our findings suggest that the cumulative burden of common genetic variation in an interacting protein network expressed in specific brain regions across the lifespan may influence susceptibility to bvFTD.
| Type: | Article |
|---|---|
| Title: | Protein network analysis reveals selectively vulnerable regions and biological processes in FTD |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1212/NXG.0000000000000266 |
| Publisher version: | https://doi.org/10.1212/NXG.0000000000000266 |
| Language: | English |
| Additional information: | Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. |
| Keywords: | All Genetics, All Cognitive Disorders/Dementia, Gene expression studies, Association studies in genetics, Frontotemporal dementia |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10058132 |
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