{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T11:22:57Z","timestamp":1787829777130,"version":"build-2784847793"},"reference-count":34,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Although genetic studies have linked immune phenotypes with anxiety, broad Mendelian randomization (MR) screens require explicit multiple-testing control. We reappraised 1753 reported immune-cell-trait-to-anxiety inverse-variance-weighted (IVW) association records available in the analysis tables and assessed the chromosome 20 signal that includes CD40. Methods: The reported records were derived from the 731-trait Sardinian flow-cytometry GWAS of Orr\u00f9 et al. and were evaluated across one UK Biobank and three FinnGen anxiety phenotypes; outcome-specific Benjamini\u2013Hochberg false-discovery-rate (FDR) correction was applied to the available analysis table. The leading locus was examined using bulk and single-cell expression quantitative trait locus annotations, two-sample MR, summary-data-based MR (SMR), HEIDI tests, and regional colocalization results. Results: Of 1753 tests, 120 were nominally significant, and 21 were retained after outcome-specific FDR correction (14 for UK Biobank anxiety and 7 for FinnGen all anxiety; none for generalized or phobic anxiety). B-cell and regulatory\/CD4 T-cell traits were common among retained associations, and several B-cell traits mapped to variants at the CD40 locus. For FinnGen all anxiety disorders, monocyte instruments gave a positive estimate (beta = 0.00418, p = 9.25 \u00d7 10\u22124), whereas three na\u00efve B-cell instruments gave a negative estimate (beta = \u22120.0520, p = 2.64 \u00d7 10\u22124). Monocyte SMR was null (p = 0.542). Na\u00efve B-cell SMR was nominally significant (p = 0.00537), but HEIDI could not be calculated. Regional colocalization was weak in both cell contexts (PP.H4 = 0.0205 and 0.00272). Conclusions: The post-selection locus follow-up prioritizes a chromosome 20 immune locus but does not establish CD40-mediated regulation of anxiety. Because the upstream screen was not regenerated from source GWAS files and complete per-instrument F-statistics were unavailable, all findings are exploratory. CD40 remains a testable candidate for ancestry-matched fine-mapping and cell-state-specific validation.<\/jats:p>","DOI":"10.3390\/genes17091018","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T10:58:21Z","timestamp":1787828301000},"page":"1018","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immune-Related Mendelian Randomization Signals for Anxiety Disorders Highlight the CD40 Locus on Chromosome 20 (chr20:46118\u201346130 Mb, GRCh38)"],"prefix":"10.3390","volume":"17","author":[{"given":"Luwei","family":"Wang","sequence":"first","affiliation":[{"name":"School of Food Engineering, Yantai Engineering Research Center of Food Green Processing and Quality Control, Ludong University, Yantai 264025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Duan","sequence":"additional","affiliation":[{"name":"School of Food Engineering, Yantai Engineering Research Center of Food Green Processing and Quality Control, Ludong University, Yantai 264025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Digital Medical Engineering, Southeast University, Nanjing 210096, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sa-ouk","family":"Kang","sequence":"additional","affiliation":[{"name":"Laboratory of Biophysics, School of Biological Sciences, Institute of Microbiology, Seoul National University, Seoul 151-742, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Ye","sequence":"additional","affiliation":[{"name":"Institute of Computational Science and Technology, Guangzhou University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Food Engineering, Yantai Engineering Research Center of Food Green Processing and Quality Control, Ludong University, Yantai 264025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1016\/S0140-6736(21)00359-7","article-title":"Anxiety disorders","volume":"397","author":"Penninx","year":"2021","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1038\/s41583-023-00729-2","article-title":"Central regulation of stress-evoked peripheral immune responses","volume":"24","author":"Chan","year":"2023","journal-title":"Nat. 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