{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T14:27:10Z","timestamp":1788532030981,"version":"build-2803163510"},"reference-count":64,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"20","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,5,15]]},"abstract":"<jats:p>\n                    IgA nephropathy (IgAN) is a common autoimmune kidney disease and a leading cause of chronic kidney disease (CKD), yet the immune cell-specific mechanisms underlying disease progression remain incompletely understood, particularly with respect to macrophage heterogeneity. We analyzed single-cell RNA sequencing (scRNA-seq) data from IgAN and CKD kidney samples to characterize macrophage subpopulations and identify differentially expressed genes. Mendelian randomization analyses using publicly available genome-wide association study data were performed as an exploratory approach to prioritize macrophage-associated genes potentially linked to IgAN risk. Bulk RNA-seq datasets were used for transcriptomic validation. In silico molecular docking was conducted to explore potential small-molecule interactions with prioritized targets. Alternatively activated macrophages were the predominant macrophage subpopulation in both IgAN and CKD samples compared with controls. Exploratory Mendelian randomization analyses highlighted several macrophage-associated genes, including\n                    <jats:italic toggle=\"yes\">RGS1<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">HLA-DPA1<\/jats:italic>\n                    , as candidates potentially linked to IgAN susceptibility. Bulk RNA-seq analyses showed downregulation of\n                    <jats:italic toggle=\"yes\">RGS1<\/jats:italic>\n                    and upregulation of\n                    <jats:italic toggle=\"yes\">HLA-DPA1<\/jats:italic>\n                    in IgAN, supporting their transcriptional relevance. Molecular docking suggested isotretinoin as a potential small-molecule interactor with RGS1, although this finding is based solely on computational prediction. This integrative, hypothesis-generating study highlights the expansion of alternatively activated macrophage in IgAN and prioritizes macrophage-associated genes that may contribute to disease susceptibility. These findings provide a computational framework for future experimental validation and mechanistic studies, rather than definitive evidence of causality or therapeutic efficacy.\n                  <\/jats:p>","DOI":"10.1097\/md.0000000000048751","type":"journal-article","created":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T02:01:02Z","timestamp":1778896862000},"page":"e48751","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Combination scRNA-seq with GWAS identifies genetic risk factors in IgA nephropathy: An observational study"],"prefix":"10.1097","volume":"105","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2131-3781","authenticated-orcid":false,"given":"Jinhua","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Kidney Transplantation, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China"},{"name":"Department of Organ Transplantation, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Kidney Transplantation, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guancan","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Urology, South China Hospital, Medical School, Shenzhen University, Shenzhen, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruojiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Kidney Transplantation, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Plastic and Cosmetic Surgery, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People\u2019s Hospital, Quzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Na","sequence":"additional","affiliation":[{"name":"Department of Kidney Transplantation, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China"},{"name":"Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaozhong","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Urology, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People\u2019s Hospital, Quzhou, Zhejiang, 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