{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T05:47:28Z","timestamp":1785822448628,"version":"3.56.0"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Inflammatory bowel disease (IBD) and IgA nephropathy (IgAN) share features of mucosal immune dysregulation, but the genetic basis of their relationship and the contribution of specific IBD subtypes remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using public genome-wide association study (GWAS) summary datasets, we performed bidirectional Mendelian randomization (MR) analyses in European and East Asian populations, together with generalized summary-data-based Mendelian randomization (GSMR), Causal Analysis Using Summary Effect Estimates (CAUSE), genetic correlation, enrichment, cross-trait locus analysis, colocalization, and single-cell RNA sequencing. Phenotypic support was assessed in a clinical cohort of 9,371 patients with IBD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Crohn\u2019s disease (CD), but not ulcerative colitis (UC), showed a consistent directional genetic association with IgAN across populations, and GSMR provided complementary support for this association (P\u00a0=\u00a04.02 \u00d7 10\n                      <jats:sup>-5<\/jats:sup>\n                      ). CAUSE did not clearly favor the causal model over the sharing model. Standard linkage disequilibrium score regression (LDSC) identified a positive genetic correlation between CD and IgAN (rg = 0.392, SE\u00a0=\u00a00.093, P\u00a0=\u00a02.53 \u00d7 10\n                      <jats:sup>-5<\/jats:sup>\n                      ), with constrained-intercept LDSC and genetic covariance analyzer (GNOVA) providing supportive evidence. Functional analyses showed enrichment in whole blood and spleen, but not kidney tissue. Integrative analyses prioritized\n                      <jats:italic>ERAP2<\/jats:italic>\n                      and\n                      <jats:italic>CARD9<\/jats:italic>\n                      as leading candidate genes, with the strongest colocalization support observed for\n                      <jats:italic>ERAP2<\/jats:italic>\n                      in sigmoid-colon expression quantitative trait locus (eQTL) data (posterior probability of colocalization [PPH4] = 90.4%) and for\n                      <jats:italic>CARD9<\/jats:italic>\n                      at the GWAS level (PPH4\u00a0=\u00a098.4%). In the clinical cohort, biopsy-confirmed IgAN was more common in CD than in UC (Firth-adjusted OR\u00a0=\u00a03.40, 95% CI 1.28\u201311.28; P\u00a0=\u00a00.0125).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      These findings support shared genetic architecture between CD and IgAN and suggest a possible directional genetic association between CD liability and IgAN risk.\n                      <jats:italic>ERAP2<\/jats:italic>\n                      and\n                      <jats:italic>CARD9<\/jats:italic>\n                      were prioritized as candidate genes within a proposed gut\u2013immune\u2013kidney framework.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1905767","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T05:38:20Z","timestamp":1785821900000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Shared genetic architecture between Crohn\u2019s disease and IgA nephropathy: implications for a gut\u2013immune\u2013kidney axis"],"prefix":"10.3389","volume":"17","author":[{"given":"Tao","family":"Su","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University","place":["Guangzhou, Guangdong, China"]},{"name":"Guangdong Provincial Clinical Research Center for Digestive Diseases","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengjun","family":"Liang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Clinical Research Center for Digestive 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Sixth Affiliated Hospital of Sun Yat-sen University","place":["Guangzhou, Guangdong, China"]},{"name":"Guangdong Provincial Clinical Research Center for Digestive Diseases","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luying","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University","place":["Guangzhou, Guangdong, China"]},{"name":"Guangdong Provincial Clinical Research Center for Digestive Diseases","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University","place":["Guangzhou, Guangdong, China"]},{"name":"Guangdong Provincial Clinical Research Center for Digestive Diseases","place":["Guangzhou, Guangdong, 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