{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T00:41:54Z","timestamp":1793234514245,"version":"4.5.0"},"reference-count":61,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["R01 DK105154"],"award-info":[{"award-number":["R01 DK105154"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["R01 DK132299"],"award-info":[{"award-number":["R01 DK132299"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["R01 DK105154"],"award-info":[{"award-number":["R01 DK105154"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["R01 DK132299"],"award-info":[{"award-number":["R01 DK132299"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"crossref","award":["K24 HL157960"],"award-info":[{"award-number":["K24 HL157960"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Science Foundation Ireland","award":["15\/IA\/3152"],"award-info":[{"award-number":["15\/IA\/3152"]}]},{"name":"Science Foundation Ireland","award":["15\/IA\/3152"],"award-info":[{"award-number":["15\/IA\/3152"]}]},{"name":"US Ireland R & D partnership award","award":["US IRL 2022-1-HRB"],"award-info":[{"award-number":["US IRL 2022-1-HRB"]}]},{"name":"US Ireland R & D partnership award","award":["US IRL 2022-1-HRB"],"award-info":[{"award-number":["US IRL 2022-1-HRB"]}]},{"DOI":"10.13039\/100020202","name":"UCD Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100020202","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100020202","name":"UCD Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100020202","id-type":"DOI","asserted-by":"crossref"}]},{"name":"George M. O\u2019Brien Michigan Kidney Translational Resource Center NIH\/NIDDK","award":["U54DK137314"],"award-info":[{"award-number":["U54DK137314"]}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec>\n                    <jats:title>Key Points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Comprehensive genome-wide association study of eGFR in diabetes, accounting for diabetes duration, kidney disease, and known modifiers, identified novel genetic effects.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Incorporation of various kidney multi-omics data provides supporting evidence for the role of novel genome-wide association study loci in diabetic kidney disease.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Diabetic kidney disease (DKD) is a serious diabetes complication caused by both environmental and genetic risk factors. Previous genome-wide association studies (GWAS) have identified several loci associated with kidney function and kidney disease in the general population and, to a lesser extent, in diabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To uncover the genetic factors driving diabetes-induced kidney function, we conducted a series of GWAS meta-analyses of eGFR in 17,267 individuals with type 1 diabetes and 35,264 with type 2 diabetes (52,531 total), using multiple well-characterized cohorts of type 1 diabetes DKD and data from the UK Biobank and SUrrogate markers for Micro- and Macrovascular hard end points for Innovative diabetes Tools (SUMMIT) consortium. We further accounted for DKD case\/control status, diabetes duration and subtype, body mass index, glycated hemoglobin levels, and the relationship between eGFR and albuminuria.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      GWAS identified 13 loci associated with eGFR (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 5\u00d710\n                      <jats:sup>\u22128<\/jats:sup>\n                      ), with five loci (candidate genes:\n                      <jats:italic toggle=\"yes\">HIPK3<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">TRIM5<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">RORA<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">ERBB4<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">BCL6<\/jats:italic>\n                      \/\n                      <jats:italic toggle=\"yes\">LPP<\/jats:italic>\n                      ) not associated with or were in opposite directions as compared with eGFR in the general population. Four candidate genes (\n                      <jats:italic toggle=\"yes\">HIPK3<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">BCL6, LPP<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">RORA<\/jats:italic>\n                      ) demonstrated evidence of differential expression in kidney compartments and cells among subgroups with DKD or diabetes versus controls. Lead single-nucleotide polymorphisms rs8027829 (\n                      <jats:italic toggle=\"yes\">RORA<\/jats:italic>\n                      ) and rs76300256 (\n                      <jats:italic toggle=\"yes\">BCL6\/LPP<\/jats:italic>\n                      ) were methylation quantitative trait loci in whole blood and kidney tissue, respectively, and rs76300256 and its related CpGs all cluster in a kidney enhancer.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our integrated approach identified candidate genes with diabetes-specific effects on kidney function.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.0000000718","type":"journal-article","created":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T12:06:10Z","timestamp":1746446770000},"page":"1939-1953","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":7,"title":["Genome-Wide Association Study of Quantitative Kidney Function in 52,531 Individuals with Diabetes Identifies Five Diabetes-Specific Loci"],"prefix":"10.1681","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9520-2788","authenticated-orcid":false,"given":"Joanne B.","family":"Cole","sequence":"first","affiliation":[{"name":"Department of Biomedical Informatics, University of Colorado School of Medicine, Aurora, Colorado"},{"name":"Programs in Metabolism and Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts"},{"name":"Center for Genomic Medicine and Diabetes Unit, Endocrine Division, Massachusetts General Hospital, Boston, Massachusetts"},{"name":"Department of Medicine, Harvard Medical School, Boston, Massachusetts"},{"name":"Division of Endocrinology, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1271-8696","authenticated-orcid":false,"given":"Emma H.","family":"Dahlstr\u00f6m","sequence":"additional","affiliation":[{"name":"Folkh\u00e4lsan Institute of Genetics, Folkh\u00e4lsan Research Center, Helsinki, Finland"},{"name":"Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland"},{"name":"Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0548-3967","authenticated-orcid":false,"given":"Damian","family":"Fermin","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4569-1741","authenticated-orcid":false,"given":"Yogesh","family":"Gupta","sequence":"additional","affiliation":[{"name":"Centre for Public Health, School of Medicine, Dentistry and Biomedical Science, Royal Victoria Hospital, Queen's University Belfast, Belfast, Northern Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2481-5162","authenticated-orcid":false,"given":"Claire","family":"Hill","sequence":"additional","affiliation":[{"name":"Centre for Public Health, School of Medicine, Dentistry and Biomedical Science, Royal Victoria Hospital, Queen's University Belfast, Belfast, Northern Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6419-4826","authenticated-orcid":false,"given":"Laura J.","family":"Smyth","sequence":"additional","affiliation":[{"name":"Centre for Public Health, School of Medicine, Dentistry and Biomedical Science, Royal Victoria Hospital, Queen's University Belfast, Belfast, Northern Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0733-8616","authenticated-orcid":false,"given":"Hongbo","family":"Liu","sequence":"additional","affiliation":[{"name":"Renal Electrolyte and Hypertension Division, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania"},{"name":"Institute of Diabetes, Obesity, and Metabolism, University of Pennsylvania, Philadelphia, Pennsylvania"},{"name":"Department of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania,"},{"name":"Penn-CHOP Kidney Innovation Center, University of Pennsylvania, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1683-323X","authenticated-orcid":false,"given":"Raymond J.","family":"Kreienkamp","sequence":"additional","affiliation":[{"name":"Programs in Metabolism and Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts"},{"name":"Center for Genomic Medicine and Diabetes Unit, Endocrine Division, Massachusetts General Hospital, Boston, Massachusetts"},{"name":"Department of Medicine, Harvard Medical School, Boston, Massachusetts"},{"name":"Division of Endocrinology, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus G.","family":"Pezzolesi","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah"},{"name":"Diabetes and Metabolism Center, University of Utah School of Medicine, Salt Lake City, Utah"},{"name":"Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah"},{"name":"Department of Nutrition and Integrative Physiology, University of Utah School of Medicine, Salt Lake City, Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9524-9567","authenticated-orcid":false,"given":"Jing Jing","family":"Cao","sequence":"additional","affiliation":[{"name":"The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0672-554X","authenticated-orcid":false,"given":"Erkka","family":"Valo","sequence":"additional","affiliation":[{"name":"Folkh\u00e4lsan Institute of Genetics, Folkh\u00e4lsan Research Center, 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S.","family":"Rich","sequence":"additional","affiliation":[{"name":"Department of Genome Sciences, University of Virginia, Charlottesville, Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4908-5474","authenticated-orcid":false,"given":"Eoin P.","family":"Brennan","sequence":"additional","affiliation":[{"name":"Diabetes Complications Research Centre, School of Medicine, UCD Conway Institute, University College Dublin, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3452-6858","authenticated-orcid":false,"given":"Darrell","family":"Andrews","sequence":"additional","affiliation":[{"name":"Diabetes Complications Research Centre, School of Medicine, UCD Conway Institute, University College Dublin, Dublin, 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Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raimund","family":"Weitgasser","sequence":"additional","affiliation":[{"name":"Competence Centre Diabetes, Diakonissen-Wehrle Hospital, Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0448-8229","authenticated-orcid":false,"given":"Jelizaveta","family":"Sokolovska","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Life Sciences, University of Latvia, Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5008-9953","authenticated-orcid":false,"given":"Lina","family":"Radzeviciene","sequence":"additional","affiliation":[{"name":"Institute of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, Kaunus, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0108-9305","authenticated-orcid":false,"given":"Rasa","family":"Verkauskiene","sequence":"additional","affiliation":[{"name":"Institute of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, Kaunus, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolae M.","family":"Panduru","sequence":"additional","affiliation":[{"name":"Carol Davila University of Medicine and Pharmacy, Bucharest, Romania"},{"name":"IMI \u2013 Center of Diabetes, Nutrition and Metabolism, Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1531-4294","authenticated-orcid":false,"given":"Peter","family":"Rossing","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center Copenhagen, Herlev, Denmark"},{"name":"Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7464-3354","authenticated-orcid":false,"given":"Tarunveer S.","family":"Ahluwalia","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center Copenhagen, Herlev, Denmark"},{"name":"Department of Biology, The Bioinformatics Center, University of Copenhagen, Copenhagen, Denmark"},{"name":"Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6181-089X","authenticated-orcid":false,"given":"Gianpaolo","family":"Zerbini","sequence":"additional","affiliation":[{"name":"Division of Immunology, Transplantation and Infectious Diseases, Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Marre","sequence":"additional","affiliation":[{"name":"Institut Necker Enfants Malades, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7110-6994","authenticated-orcid":false,"given":"Samy","family":"Hadjadj","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, L'institut du thorax, INSERM,CHU Nantes, CNRS, Nantes Universit\u00e9, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9303-3810","authenticated-orcid":false,"given":"Tina","family":"Costacou","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University of Pittsburgh Public Health, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1845-8477","authenticated-orcid":false,"given":"Rachel 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Center for Diabetes, University of Colorado School of Medicine, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6082-5934","authenticated-orcid":false,"given":"Maria Luiza","family":"Caramori","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Cleveland Clinic Foundation, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7301-9616","authenticated-orcid":false,"given":"Michael","family":"Mauer","sequence":"additional","affiliation":[{"name":"Divisions of Nephrology, Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5241-514X","authenticated-orcid":false,"given":"Kerstin","family":"Brismar","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Surgery, 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Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1005-3726","authenticated-orcid":false,"given":"Katalin","family":"Susztak","sequence":"additional","affiliation":[{"name":"Renal Electrolyte and Hypertension Division, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania"},{"name":"Institute of Diabetes, Obesity, and Metabolism, University of Pennsylvania, Philadelphia, Pennsylvania"},{"name":"Department of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania,"},{"name":"Penn-CHOP Kidney Innovation Center, University of Pennsylvania, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4064-0582","authenticated-orcid":false,"given":"Matthias","family":"Kretzler","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, 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