{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T12:49:58Z","timestamp":1792586998075,"version":"4.5.0"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","funder":[{"DOI":"10.13039\/501100000156","name":"Fonds de Recherche du Qu\u00e9bec \u2013 Sant\u00e9","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000156","id-type":"DOI","asserted-by":"publisher"}]},{"name":"UK Biobank","award":["48839"],"award-info":[{"award-number":["48839"]}]},{"name":"UK Biobank","award":["66222"],"award-info":[{"award-number":["66222"]}]},{"name":"Toronto General Hospital Foundation"},{"DOI":"10.13039\/501100000035","name":"Institute of Nutrition, Metabolism and Diabetes","doi-asserted-by":"publisher","award":["201909PJ9 and 202003PJT"],"award-info":[{"award-number":["201909PJ9 and 202003PJT"]}],"id":[{"id":"10.13039\/501100000035","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019217","name":"Institut de valorisation des donn\u00e9es","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100019217","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009268","name":"Alport Syndrome Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000156","name":"FRQS","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000156","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["CJASN"],"published-print":{"date-parts":[[2022,5]]},"abstract":"\n Background and objectives<\/jats:title>\n Glomerular hematuria has varied causes but can have a genetic basis, including Alport syndrome and IgA nephropathy.<\/jats:p>\n <\/jats:sec>\n \n Design, setting, participants, & measurements<\/jats:title>\n \n We used summary statistics to identify genetic variants associated with hematuria in White British UK Biobank participants. Individuals with glomerular hematuria were enriched by excluding participants with genitourinary conditions. A strongly associated locus on chromosome 2 (\n COL4A4<\/jats:italic>\n -\n COL4A3<\/jats:italic>\n ) was identified. The region was reimputed using the Trans-Omics for Precision Medicine Program followed by sequential rounds of regional conditional analysis, conditioning on previous genetic signals. Similarly, we applied conditional analysis to identify independent variants in the MHC region on chromosome 6 using imputed\n HLA<\/jats:italic>\n haplotypes.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n In total, 16,866 hematuria cases and 391,420 controls were included. Cases had higher urinary albumin-creatinine compared with controls (women: 13.01 mg\/g [8.05\u201321.33] versus 12.12 mg\/g [7.61\u201319.29];\n P<\/jats:italic>\n <0.001; men: 8.85 mg\/g [5.66\u201316.19] versus 7.52 mg\/g [5.04\u201312.39];\n P<\/jats:italic>\n <0.001) and lower eGFR (women: 88\u00b114 versus 90\u00b113 ml\/min per 1.72 m\n 2<\/jats:sup>\n ;\n P<\/jats:italic>\n <0.001; men: 87\u00b115 versus 90\u00b113 ml\/min per 1.72 m\n 2<\/jats:sup>\n ;\n P<\/jats:italic>\n <0.001), supporting enrichment of glomerular hematuria. Variants at six loci (\n PDPN<\/jats:italic>\n ,\n COL4A4-COL4A3<\/jats:italic>\n ,\n HLA-B<\/jats:italic>\n ,\n SORL1<\/jats:italic>\n ,\n PLLP<\/jats:italic>\n , and\n TGFB1<\/jats:italic>\n ) met genome-wide significance (\n P<\/jats:italic>\n <5E-8). At chromosome 2,\n COL4A4<\/jats:italic>\n p.Ser969X (rs35138315; minor allele frequency=0.00035;\n P<\/jats:italic>\n <7.95E-35; odds ratio, 87.3; 95% confidence interval, 47.9 to 159.0) had the most significant association, and two variants in the locus remained associated with hematuria after conditioning for this variant:\n COL4A3<\/jats:italic>\n p.Gly695Arg (rs200287952; minor allele frequency=0.00021;\n P<\/jats:italic>\n <2.16E-7; odds ratio, 45.5; 95% confidence interval, 11.8 to 168.0) and a common\n COL4A4<\/jats:italic>\n intron 25 variant (not previously reported; rs58261427; minor allele frequency=0.214;\n P<\/jats:italic>\n <2.00E-9; odds ratio, 1.09; 95% confidence interval, 1.06 to 1.12). Of the\n HLA<\/jats:italic>\n haplotypes,\n HLA-B<\/jats:italic>\n (\n *0801<\/jats:italic>\n ; minor allele frequency=0.14;\n P<\/jats:italic>\n <4.41E-24; odds ratio, 0.84; 95% confidence interval, 0.82 to 0.88) displayed the most statistically significant association. For remaining loci, we identified three novel associations, which were replicated in the deCODE dataset for dipstick hematuria (nearest genes:\n PDPN<\/jats:italic>\n ,\n SORL1<\/jats:italic>\n , and\n PLLP<\/jats:italic>\n ).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Our study identifies six loci associated with hematuria, including independent variants in\n COL4A4<\/jats:italic>\n -\n COL4A3<\/jats:italic>\n and\n HLA-B<\/jats:italic>\n . Additionally, three novel loci are reported, including an association with an intronic variant in\n PDPN<\/jats:italic>\n expressed in the podocyte.\n <\/jats:p>\n <\/jats:sec>\n \n Podcast<\/jats:title>\n This article contains a podcast at https:\/\/www.asn-online.org\/media\/podcast\/CJASN\/2022_04_26_CJN13711021.mp3<\/jats:p>\n <\/jats:sec>","DOI":"10.2215\/cjn.13711021","type":"journal-article","created":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T14:36:30Z","timestamp":1651847790000},"page":"672-683","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":20,"title":["GWAS of Hematuria"],"prefix":"10.2215","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1306-1868","authenticated-orcid":false,"given":"Sarah A.","family":"Gagliano Taliun","sequence":"first","affiliation":[{"name":"Department of Medicine, Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada"},{"name":"Department of Neurosciences, 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Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1676-864X","authenticated-orcid":false,"given":"Kari","family":"Stefansson","sequence":"additional","affiliation":[{"name":"deCODE Genetics\/Amgen, Inc., Reykjavik, Iceland"},{"name":"Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9169-118X","authenticated-orcid":false,"given":"Andrew D.","family":"Paterson","sequence":"additional","affiliation":[{"name":"Division of Epidemiology, Dalla Lana School of Public Health, Toronto, Ontario, Canada"},{"name":"Division of Biostatistics, Dalla Lana School of Public Health, Toronto, Ontario, Canada"},{"name":"Genetics and Genome Biology, Research Institute at The Hospital for Sick Children, Toronto, Ontario, Canada"},{"name":"Institute of Medical Sciences, University of Toronto, Toronto, Ontario, 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