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The role of Immune cells in obesity has been recently recognized, whereas its translation into therapy requires identifying key target genes. We performed Mendelian randomization (MR) analysis to assess causal relationships between expression quantitative trait loci (eQTL) of 14 immune cells and obesity\u2010related traits (obesity, body mass index and body fat percentage), and validated the results in colocalization analysis. For the putative causal genes identified by the MR and colocalization analyses, we conducted pathway enrichment, differential expressed gene (DEG) analysis and search of druggable evidence, and utilized a Tier system to prioritize drug targets for obesity. MR and colocalization evidence was observed for 1630 genes associated with one or more obesity\u2010related traits, mainly expressed in CD4\n                    <jats:sup>+<\/jats:sup>\n                    naive\/central memory T cells and enriched in antigen processing and presentation pathways. Forty\u2010one genes showed causal relationship with all three outcomes, among which 19 genes have not been reported for obesity previously. DEG analysis using single\u2010cell RNA sequencing data of blood or adipose tissue indicated that the differential expression of\n                    <jats:italic>UBE2Z<\/jats:italic>\n                    in monocytes,\n                    <jats:italic>ZCCHC7<\/jats:italic>\n                    in T cells, and\n                    <jats:italic>FNBP4<\/jats:italic>\n                    in B cells between lean and obese individuals were consistent with the MR results. By searching drug\u2010gene interaction databases, we found targeted drugs for\n                    <jats:italic>PYGB<\/jats:italic>\n                    and\n                    <jats:italic>PRUNE1<\/jats:italic>\n                    , and\n                    <jats:italic>PYGB<\/jats:italic>\n                    was the top gene ranked in the Tier system. This study provides evidence for the involvement of immune cells in obesity, and the potential cell\u2010specific, immune\u2010related targets for obesity treatment.\n                  <\/jats:p>","DOI":"10.1111\/jcmm.71185","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T12:18:32Z","timestamp":1778588312000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Single\u2010Cell Transcriptome\u2010Wide Mendelian Randomization and Colocalization Uncover Potential Immunocytes\u2010Related Therapeutic Targets for Obesity"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5423-963X","authenticated-orcid":false,"given":"Xingjian","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Beijing Chao\u2010Yang Hospital Capital Medical University  Beijing People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Beijing Chao\u2010Yang Hospital Capital Medical University  Beijing People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoying","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Beijing Chao\u2010Yang Hospital Capital Medical University  Beijing People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Beijing Chao\u2010Yang Hospital Capital Medical University  Beijing People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0429-5748","authenticated-orcid":false,"given":"Jia","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Beijing Chao\u2010Yang Hospital Capital Medical University  Beijing People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9321-5200","authenticated-orcid":false,"given":"Guang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Beijing Chao\u2010Yang Hospital Capital Medical University  Beijing People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,5,12]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/joim.13816"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.2337\/dci23-0100"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)02403-5"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature21363"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03830-7"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-025-01989-7"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2022.12.011"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehad736"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2023.09.016"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abf3041"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2026.116330"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2025.105596"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41531-025-01148-z"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-53621-7"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007081"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05473-8"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddy327"},{"key":"e_1_2_13_19_1","doi-asserted-by":"crossref","unstructured":"K. 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