{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T03:20:18Z","timestamp":1787800818552,"version":"build-2784847793"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T00:00:00Z","timestamp":1771804800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002865","name":"Chongqing Science and Technology Bureau","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002865","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Health Commission Foundation","award":["2023GGXM001"],"award-info":[{"award-number":["2023GGXM001"]}]},{"DOI":"10.13039\/501100004374","name":"Chongqing Medical University","doi-asserted-by":"publisher","award":["NCRCCHD-2023-MP-01"],"award-info":[{"award-number":["NCRCCHD-2023-MP-01"]}],"id":[{"id":"10.13039\/501100004374","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2705101"],"award-info":[{"award-number":["2022YFC2705101"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Program for Youth Innovation in Future Medicine","award":["W0098"],"award-info":[{"award-number":["W0098"]}]},{"name":"Project of Science and Technology Research of Chongqing Education Commission","award":["KJZD-M202200401"],"award-info":[{"award-number":["KJZD-M202200401"]}]},{"name":"Postdoctoral Fund of Chongqing Natural Science Foundation","award":["CSTB2022NSCQ-BHX0653"],"award-info":[{"award-number":["CSTB2022NSCQ-BHX0653"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,27]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Steroid-sensitive nephrotic syndrome (SSNS) is a relatively rare glomerular disease with considerable clinical and genetic heterogeneity. Although efforts have been made to explore the genetic determinants of SSNS, the underlying genetic architecture has still been hampered by limited sample size and remains to be elucidated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a genome-wide association study involving 510 sporadic pediatrics of SSNS and 1062 controls with Chinese ancestry, followed by a transethnic meta-analysis involving 2942 cases and 37\u2009041 controls. We evaluated the colocalization probability between single-cell expression quantitative trait loci, plasma protein quantitative trait loci, and the novel loci using the colocalization method. We explored the potential causal effects using Mendelian randomization (MR) and assessed the clinical associations of polygenic risk scores (PRS) for SSNS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Two novel genome-wide significant signals, rs4309200 from M6PR-KLRG1 (P\u00a0=\u00a04.70\u00a0\u00d7\u00a010\u22129, OR\u00a0=\u00a01.23, 95%CI\u00a0=\u00a01.16\u20131.30) and rs9303279 from GSDMB-ORMDL3 (P\u00a0=\u00a07.25\u00a0\u00d7\u00a010\u22129, OR\u00a0=\u00a00.82, 95%CI\u00a0=\u00a00.75\u20130.89), both highly related to immunological function, were identified for SSNS. Colocalization and MR analyses revealed that a genetic tendency toward higher M6PR expression in NK and CD4+ T cells with an effector memory or central memory phenotype (CD4 ET) was associated with an increased risk of SSNS (NK: PPH4\u00a0=\u00a00.93; P\u00a0=\u00a02.04\u00a0\u00d7\u00a010\u22124, OR\u00a0=\u00a01.60; CD4 ET: PPH4\u00a0=\u00a00.91; P\u00a0=\u00a08.14\u00a0\u00d7\u00a010\u22123, OR\u00a0=\u00a02.28), whereas higher ORMDL3 expression in B memory and CD4 ET cells was associated with a lower risk of SSNS (B memory: PPH4\u00a0=\u00a00.93; P\u00a0=\u00a03.83\u00a0\u00d7\u00a010\u22128, OR\u00a0=\u00a00.61; CD4 ET: PPH4\u00a0=\u00a00\/92; P\u00a0=\u00a01.82\u00a0\u00d7\u00a010\u22129, OR\u00a0=\u00a00.49). The clinical correlation analysis confirmed that a higher PRS is associated with an earlier age of onset, and the rs56117924 from the NPHS1 gene may predominantly drive this association.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We identified two novel immune-related loci associated with susceptibility to SSNS, nominating M6PR and ORMDL3 as potential contributors to SSNS risk in a cell-type-specific manner, and confirmed the association of PRS with earlier disease onset. These findings expand our knowledge of the genetic architecture of SSNS and highlight the importance of large-scale collaborations in uncovering genetic associations related to SSNS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ndt\/gfag041","type":"journal-article","created":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T12:33:38Z","timestamp":1771763618000},"page":"1629-1641","source":"Crossref","is-referenced-by-count":0,"title":["Novel immune-related susceptibility loci associated with pediatric steroid-sensitive nephrotic syndrome identified by a transethnic genome-wide association study"],"prefix":"10.1093","volume":"41","author":[{"given":"Xueying","family":"Yang","sequence":"first","affiliation":[{"name":"Children\u2019s Hospital of Chongqing Medical University, National Clinical Research Center for Children and Adolescents' Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key laboratory of Pediatric 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Guangdong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wang","sequence":"additional","affiliation":[{"name":"Chengdu Women and Children Central Hospital, Chengdu Department of Nephrology, , Sichuan ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenfen","family":"Ni","sequence":"additional","affiliation":[{"name":"Shenzhen Children\u2019s Hospital Department of Nephrology, , Shenzhen, Guangdong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Liang","sequence":"additional","affiliation":[{"name":"The University of Hong Kong - Shenzhen Hospital Department of Pediatrics, , Shenzhen, Guangdong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Zhao","sequence":"additional","affiliation":[{"name":"Kunming Children\u2019s Hospital, Kunming Medical University, Kunming Department of Nephrology, , Yunnan 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