{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T03:29:22Z","timestamp":1786418962962,"version":"build-2736575974"},"reference-count":68,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T00:00:00Z","timestamp":1784332800000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32471519"],"award-info":[{"award-number":["32471519"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32571690"],"award-info":[{"award-number":["32571690"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Clinical and epidemiological evidence has suggested a potential association between kidney dysfunction and bladder cancer (BC). One hypothesis for this comorbidity is the presence of a common genetic etiology. However, little is known about the shared genetics and causality of this association. Thus, we aimed to investigate shared genetic architecture and the causal link between kidney dysfunction and bladder cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Leveraging summary statistics from large\u2010scale genome\u2010wide association studies (GWASs) conducted on European\u2010ancestry populations on eGFRcrea (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u20091,004,040), eGFRcys (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u2009460,826), BUN (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u2009852,678), UACR (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u2009288,649), urate (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u2009547,361) and BC (N\n                      <jats:sub>cases<\/jats:sub>\n                      \u2009=\u20093357, N\n                      <jats:sub>controls<\/jats:sub>\n                      \u2009=\u2009628,027), we conducted a large\u2010scale genome\u2010wide cross\u2010trait study to determine genetic overlap, to identify shared loci, and to infer causal relationships. We evaluated genetic correlation through linkage disequilibrium score regression (LDSC). Integration of single\u2010trait GWAS was accomplished by multi\u2010trait analysis of GWAS (MTAG), which enabled cross\u2010trait meta\u2010analysis to unveil overlapping genetic loci between five kidney function traits and BC. Shared genes were further validated through colocalization analysis and transcriptome\u2010wide association analysis. Bidirectional Mendelian Randomization (MR) was conducted to determine causal inference of kidney function traits on BC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found positive correlations between both BUN and urate and BC at the genome\u2010wide level. A total of 157 significant overlapping genetic loci (range 7 to 72) were identified across five kidney function traits and BC. Among them,\n                      <jats:italic>PSCA<\/jats:italic>\n                      was prioritized as the strongest shared gene with support from MTAG, colocalization, and TWAS, whereas\n                      <jats:italic>ZFHX3, TTC33<\/jats:italic>\n                      , and\n                      <jats:italic>ATP2A1<\/jats:italic>\n                      were considered candidates supported only by MTAG and TWAS. MR provided the most consistent support for a potential positive causal effect of BUN on BC, limited support for UACR, and exploratory evidence for urate.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our cross\u2010trait analysis demonstrated a shared genetic basis underlying kidney function and BC, providing novel insights into the biological functions and molecular mechanisms underlying these complex traits.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.72025","type":"journal-article","created":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T09:06:17Z","timestamp":1784365577000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Shared Genetics of Kidney Function Traits and Bladder Cancer: A Genome\u2010Wide Cross\u2010Trait Analysis"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3184-9213","authenticated-orcid":false,"given":"Yifei","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Urology, Lab of Health Data Science, Innovation Institute for Integration of Medicine and Engineering, Frontiers Science Center for Disease\u2010Related Molecular Network, Med\u2010X Center for Manufacturing, West China Hospital Sichuan University  Chengdu Sichuan China"},{"name":"Department of Epidemiology Harvard T.H. 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