{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T09:38:38Z","timestamp":1793180318206,"version":"4.5.0"},"reference-count":115,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Gen. Psychiatry"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Alzheimer's disease (AD), the most prevalent form of dementia, is highly heritable, yet much of its genetic basis remains unexplained. Most genetic studies have focused on European populations, with limited data from under\u2010represented groups. Whole\u2010exome sequencing (WES) in the Han Chinese population may help identify novel rare variants and population\u2010specific genetic risk factors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>This study aims to use WES to identify potential candidate genes associated with dementia and AD in the Han Chinese population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this exploratory pilot study, we performed WES in 63 Han Chinese patients with dementia, including 43 with AD and 20 with non\u2010AD dementia (including one with dementia with Lewy bodies, one with Parkinson's dementia, four with frontotemporal dementia and 14 with mixed dementia), to identify rare coding variants. Gene\u2010based case\u2013control burden analyses using public gnomAD controls were conducted in the overall dementia cohort and the AD subgroup. Protein\u2013protein interaction, functional enrichment, weighted gene coexpression network analysis (WGCNA) and gene set variation analysis (GSVA) using single\u2010nucleus RNA sequencing (snRNA\u2010seq) datasets were performed to evaluate biological relevance and cell\u2010type\u2010specific activity. Cell\u2010type marker enrichment analysis was used to identify relevant neuronal subtypes. Multilevel evidence was integrated to prioritise candidate risk genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified suggestive rare variant signals in genes involved in cilia\u2010related pathways, with stronger signals in the AD subgroup. These candidate genes were enriched in WGCNA modules associated with ageing, microtubule organisation and dementia pathology. GSVA showed increased activity of candidate genes in astrocytes using the snRNA\u2010seq dataset. Cell\u2010type marker analysis revealed strong enrichment in Ex6 excitatory neurons. Finally, integration of multilevel evidence prioritised 10 candidate genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This pilot study provides preliminary evidence that cilia\u2010related pathways may be involved in dementia, especially AD susceptibility in the Han Chinese population. Further validation in larger independent cohorts with ancestry\u2010matched controls and in functional experiments is required. Larger sample sizes for each dementia subtype will improve the detection of both dementia\u2010shared and subtype\u2010specific signals.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/gps3.70062","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T13:00:47Z","timestamp":1792587647000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Astrocyte\u2010enriched and cilia\u2010related genetic signatures in dementia: A whole\u2010exome sequencing study"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2058-8764","authenticated-orcid":false,"given":"Miaohan","family":"Deng","sequence":"first","affiliation":[{"name":"Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, School of Biomedical Engineering Shanghai Jiao Tong University  Shanghai 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