{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:12:56Z","timestamp":1787019176316,"version":"build-2736575974"},"reference-count":78,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Microglia play a central role in Alzheimer's disease (AD) pathogenesis, yet it remains unclear whether microglia-related gene expression changes contribute causally to disease risk or reflect downstream responses to neurodegeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed to systematically identify microglia-expressed genes with genetically regulated expression associated with AD risk and to characterize their functional relevance through integrative genomic analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We compiled 2454 microglia-associated genes from four transcriptomic studies and five expression databases. Using brain cis-eQTL data from PsychENCODE (n\u2009=\u20091387), we performed summary-data-based Mendelian randomization (SMR) and HEIDI tests with AD GWAS data (111,326 cases, 677,663 controls). Significant SMR signals (FDR &lt; 0.05) were evaluated using Bayesian colocalization. Regulatory context was assessed via overlap with PU.1-associated chromatin features, and differential expression was examined using single-nucleus RNA-seq from AD brains.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      SMR identified 16 genes whose genetically predicted expression was associated with AD risk (FDR &lt; 0.05), including\n                      <jats:italic toggle=\"yes\">TSPAN14<\/jats:italic>\n                      (OR = 1.10, 95% CI: 1.07\u20131.13) and\n                      <jats:italic toggle=\"yes\">GRN<\/jats:italic>\n                      (OR = 0.90, 0.86\u20130.95). Colocalization supported shared causal variants at eight loci (PPH4\u2009&gt;\u20090.8; e.g.,\n                      <jats:italic toggle=\"yes\">BLNK<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">SIGLEC11<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">CASS4<\/jats:italic>\n                      ). Most prioritized genes overlapped with PU.1-associated regulatory regions. Single-nucleus RNA-seq confirmed dysregulation of several candidates (e.g.,\n                      <jats:italic toggle=\"yes\">USP6NL<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">MS4A4A<\/jats:italic>\n                      ) in AD microglia.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We identify microglia-expressed genes with genetic evidence consistent with a potential causal role in AD. These genes are enriched in microglia-specific regulatory elements and exhibit transcriptional alterations in AD, highlighting microglial pathways as potential therapeutic targets.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877261452242","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T09:29:42Z","timestamp":1780392582000},"page":"647-658","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrative genomic and transcriptomic analysis identifies microglia-expressed genes with causal links to Alzheimer's disease risk"],"prefix":"10.1177","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0248-6101","authenticated-orcid":false,"given":"Yuanyuan","family":"Zhao","sequence":"first","affiliation":[{"name":"Shandong University of Traditional Chinese Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conghui","family":"Liu","sequence":"additional","affiliation":[{"name":"Shandong University of Traditional Chinese Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keke","family":"Yv","sequence":"additional","affiliation":[{"name":"Shandong University of Traditional Chinese Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Wang","sequence":"additional","affiliation":[{"name":"Shandong University of Traditional Chinese Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuowei","family":"Li","sequence":"additional","affiliation":[{"name":"Shandong University of Traditional Chinese Medicine"},{"name":"Affiliated Hospital of Shandong University of Traditional Chinese Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13809"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/procel\/pwae026"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01484-7"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-023-02853-3"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2024.08.003"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2023.02.033"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4397"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0145-x"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4222"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-022-02637-1"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23458"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232112990"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2024.102515"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-020-00435-y"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2025.04.029"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells11152383"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.05.018"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19737-2"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2021.11.006"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-017-0184-x"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-022-08584-8"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-019-0385-z"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4597"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aal3222"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2015.04.008"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23572"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1860-14.2014"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/database\/baz046"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac947"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1260419"},{"key":"e_1_3_3_32_2","article-title":"CZ CELLxGENE Discover: a single-cell data platform for scalable exploration, analysis and modeling of aggregated data","volume":"53","author":"Abdulla S","year":"2025","unstructured":"Abdulla S, Aevermann B, et al. 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