{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:00:58Z","timestamp":1772118058385,"version":"3.50.1"},"reference-count":78,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T00:00:00Z","timestamp":1754265600000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The influence of immune cell traits (ICTs) on the onset of multiple brain diseases has been previously investigated; however, it is limited by the sample size or colocalization evidence. Besides, the impact remains inconclusive.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a Mendelian randomization (MR) study to elucidate the causal correlation between significant ICTs and diverse brain disorders and explored the biomarkers linked to glioblastoma (GBM), a form of solid tumor, by integrating expression quantitative trait locus (eQTL) and single\u2010cell RNA sequencing (scRNA\u2010seq) analyses. The nonnegative matrix factorization (NMF) method was utilized to reclassify malignant cells into distinct cell states. Related functional analyses at the scRNA\u2010seq level were also performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We examined 731 ICTs across 13 brain disorders; impacts from these ICTs varied a lot across different brain diseases. Such ICTs mainly involved T\/natural killer (NK) cell activation, B cell differentiation, and myeloid cell suppression or activation. Pleiotropy or heterogeneity in current results has been checked and excluded via sensitivity analyses. Specifically, colocalization analyses demonstrated protective roles of distinct ICTs in T\/B\/NK cell panels for amyotrophic lateral sclerosis (ALS) and GBM, while myeloid and human leukocyte antigen (HLA)\u2010associated traits were associated with increased risk of Alzheimer's disease (AD), and then two memory cell traits were linked to the increased risk of major depressive disease (MDD). By NMF, we identified six distinct cell states within GBM cells. Furthermore, we established an eight\u2010marker glioblastoma risk signature (GBRS) using scRNA\u2010seq and eQTL data, with higher GBRS scores observed in the NFkB cluster and EGFR cluster, indicating their highlighted aggression among malignant cells. Epigallocatechin gallate could be an effective treatment candidate targeting the EGFR cluster via markers of\n                      <jats:italic>SQLE<\/jats:italic>\n                      and\n                      <jats:italic>VCP<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings identified causal effects of distinct ICTs on both malignant and nonmalignant brain diseases and underscored the pivotal role of neuroinflammation in their etiology. With combined evidence from eQTL and scRNA\u2010seq, GBM could be better characterized and managed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.70632","type":"journal-article","created":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T05:15:41Z","timestamp":1754370941000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Causal Association Between Immune Cell Traits and Risk of Multiple Malignant and Nonmalignant CNS Diseases: A Mendelian Randomization and Single\u2010Cell Transcriptomic Analysis"],"prefix":"10.1002","volume":"15","author":[{"given":"Shanbao","family":"Ke","sequence":"first","affiliation":[{"name":"Department of Oncology, Henan Provincial People's Hospital Zhengzhou University People's Hospital, Henan University People's Hospital  Zhengzhou 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