{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T23:30:07Z","timestamp":1790983807130,"version":"4.1.0"},"reference-count":48,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,20]],"date-time":"2021-03-20T00:00:00Z","timestamp":1616198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017510","name":"UK Dementia Research Institute","doi-asserted-by":"publisher","award":["MC_PC_17112"],"award-info":[{"award-number":["MC_PC_17112"]}],"id":[{"id":"10.13039\/501100017510","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Late-onset Alzheimer\u2019s 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.<\/jats:p>","DOI":"10.3390\/genes12030443","type":"journal-article","created":{"date-parts":[[2021,3,21]],"date-time":"2021-03-21T22:00:37Z","timestamp":1616364037000},"page":"443","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["The Impact of Complement Genes on the Risk of Late-Onset Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7609-7529","authenticated-orcid":false,"given":"Sarah M.","family":"Carpanini","sequence":"first","affiliation":[{"name":"UK Dementia Research Institute at Cardiff University, School of Medicine, Cardiff, CF24 4HQ, UK"},{"name":"Division of Infection and Immunity, School of Medicine, Systems Immunity Research Institute, Cardiff University, Cardiff, CF14 4XN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3225-0069","authenticated-orcid":false,"given":"Janet C.","family":"Harwood","sequence":"additional","affiliation":[{"name":"Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, CF24 4HQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Baker","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at Cardiff University, School of Medicine, Cardiff, CF24 4HQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Torvell","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at Cardiff University, School of Medicine, Cardiff, CF24 4HQ, UK"},{"name":"Division of Infection and Immunity, School of Medicine, Systems Immunity Research Institute, Cardiff University, Cardiff, CF14 4XN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"The GERAD1 Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3885-1199","authenticated-orcid":false,"given":"Rebecca","family":"Sims","sequence":"additional","affiliation":[{"name":"Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, CF24 4HQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Williams","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at Cardiff University, School of Medicine, Cardiff, CF24 4HQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4075-7676","authenticated-orcid":false,"given":"B. Paul","family":"Morgan","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at Cardiff University, School of Medicine, Cardiff, CF24 4HQ, UK"},{"name":"Division of Infection and Immunity, School of Medicine, Systems Immunity Research Institute, Cardiff University, Cardiff, CF14 4XN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1136\/bmj.327.7407.128","article-title":"Effect of Non-Steroidal Anti-Inflammatory Drugs on Risk of Alzheimer\u2019s Disease: Systematic Review and Meta-Analysis of Observational Studies","volume":"327","author":"Etminan","year":"2003","journal-title":"BMJ"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"707","DOI":"10.3233\/JAD-160420","article-title":"Complement Biomarkers as Predictors of Disease Progression in Alzheimer\u2019s Disease","volume":"54","author":"Hakobyan","year":"2016","journal-title":"J. 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