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Article

The Impact of Complement Genes on the Risk of Late-Onset Alzheimer’s Disease

1
UK Dementia Research Institute at Cardiff University, School of Medicine, Cardiff, CF24 4HQ, UK
2
Division of Infection and Immunity, School of Medicine, Systems Immunity Research Institute, Cardiff University, Cardiff, CF14 4XN, UK
3
Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, CF24 4HQ, UK
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Data used in the preparation of this article were obtained from the Genetic and Environmental Risk for Alzheimer’s disease (GERAD1) Consortium. As such, the investigators within the GERAD1 consortia contributed to the design and implementation of GERAD1 and/or provided data but did not participate in analysis or writing of this report. A full list of GERAD1 investigators and their affiliations is included in Supplementary File S1.
Academic Editors: Laura Ibanez and Justin Miller
Genes 2021, 12(3), 443; https://doi.org/10.3390/genes12030443
Received: 27 February 2021 / Revised: 13 March 2021 / Accepted: 16 March 2021 / Published: 20 March 2021
(This article belongs to the Special Issue Genetics of Alzheimer’s Disease)
Late-onset Alzheimer’s disease (LOAD), the most common cause of dementia, and a huge global health challenge, is a neurodegenerative disease of uncertain aetiology. To deliver effective diagnostics and therapeutics, understanding the molecular basis of the disease is essential. Contemporary large genome-wide association studies (GWAS) have identified over seventy novel genetic susceptibility loci for LOAD. Most are implicated in microglial or inflammatory pathways, bringing inflammation to the fore as a candidate pathological pathway. Among the most significant GWAS hits are three complement genes: CLU, encoding the fluid-phase complement inhibitor clusterin; CR1 encoding complement receptor 1 (CR1); and recently, C1S encoding the complement enzyme C1s. Complement activation is a critical driver of inflammation; changes in complement genes may impact risk by altering the inflammatory status in the brain. To assess complement gene association with LOAD risk, we manually created a comprehensive complement gene list and tested these in gene-set analysis with LOAD summary statistics. We confirmed associations of CLU and CR1 genes with LOAD but showed no significant associations for the complement gene-set when excluding CLU and CR1. No significant association with other complement genes, including C1S, was seen in the IGAP dataset; however, these may emerge from larger datasets. View Full-Text
Keywords: complement; complement receptor 1; clusterin; late-onset Alzheimer’s disease; genetics; neuroinflammation complement; complement receptor 1; clusterin; late-onset Alzheimer’s disease; genetics; neuroinflammation
MDPI and ACS Style

Carpanini, S.M.; Harwood, J.C.; Baker, E.; Torvell, M.; The GERAD1 Consortium; Sims, R.; Williams, J.; Morgan, B.P. The Impact of Complement Genes on the Risk of Late-Onset Alzheimer’s Disease. Genes 2021, 12, 443. https://doi.org/10.3390/genes12030443

AMA Style

Carpanini SM, Harwood JC, Baker E, Torvell M, The GERAD1 Consortium, Sims R, Williams J, Morgan BP. The Impact of Complement Genes on the Risk of Late-Onset Alzheimer’s Disease. Genes. 2021; 12(3):443. https://doi.org/10.3390/genes12030443

Chicago/Turabian Style

Carpanini, Sarah M., Janet C. Harwood, Emily Baker, Megan Torvell, The GERAD1 Consortium, Rebecca Sims, Julie Williams, and B. P. Morgan. 2021. "The Impact of Complement Genes on the Risk of Late-Onset Alzheimer’s Disease" Genes 12, no. 3: 443. https://doi.org/10.3390/genes12030443

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