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Genomics implicates adaptive and innate immunity in Alzheimer's and Parkinson's diseases

Gagliano, SA; Pouget, JG; Hardy, J; Knight, J; Barnes, MR; Ryten, M; Weale, ME; (2016) Genomics implicates adaptive and innate immunity in Alzheimer's and Parkinson's diseases. Annals of Clinical and Translational Neurology , 3 (12) pp. 924-933. 10.1002/acn3.369. Green open access

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Abstract

OBJECTIVES: We assessed the current genetic evidence for the involvement of various cell types and tissue types in the etiology of neurodegenerative diseases, especially in relation to the neuroinflammatory hypothesis of neurodegenerative diseases. METHODS: We obtained large-scale genome-wide association study (GWAS) summary statistics from Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS). We used multiple sclerosis (MS), an autoimmune disease of the central nervous system, as a positive control. We applied stratified LD score regression to determine if functional marks for cell type and tissue activity, and gene-set lists were enriched for genetic heritability. We compared our results to those from two gene-set enrichment methods (Ingenuity Pathway Analysis and enrichr). RESULTS: There were no significant heritability enrichments for annotations marking genes active within brain regions, but there were significant heritability enrichments for annotations marking genes active within cell types that form part of both the innate and adaptive immune systems. We found this for MS (as expected) and also for AD and PD. The strongest signals were from the adaptive immune system (e.g., T cells) for PD, and from both the adaptive (e.g., T cells) and innate (e.g., CD14: a marker for monocytes, and CD15: a marker for neutrophils) immune systems for AD. Annotations from the liver were also significant for AD. Pathway analysis provided complementary results. INTERPRETATION: For AD and PD, we found significant enrichment of heritability in annotations marking gene activity in immune cells.

Type: Article
Title: Genomics implicates adaptive and innate immunity in Alzheimer's and Parkinson's diseases
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/acn3.369
Publisher version: http://doi.org/10.1002/acn3.369
Language: English
Additional information: © 2016 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: Science & Technology, Life Sciences & Biomedicine, Clinical Neurology, Neurosciences, Neurosciences & Neurology, CENTRAL-NERVOUS-SYSTEM, LIVER-X-RECEPTORS, WIDE ASSOCIATION, MULTIPLE-SCLEROSIS, NEURODEGENERATIVE DISEASE, AUTOIMMUNE-DISEASES, HUMAN BRAIN, METAANALYSIS, ENRICHMENT, EXPRESSION
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 Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept
URI: https://discovery.ucl.ac.uk/id/eprint/1537220
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