{"entity": "publication", "iuid": "1709ae2a29f648c1b91bf3572239c1c9", "timestamp": "2026-08-16T09:46:20.169Z", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1709ae2a29f648c1b91bf3572239c1c9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1709ae2a29f648c1b91bf3572239c1c9"}}, "title": "Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline.", "authors": [{"family": "Gorski", "given": "Mathias", "initials": "M", "orcid": "0000-0003-2229-1120", "researcher": {"href": "https://publications.scilifelab.se/researcher/ebc59079554842ecb3512ef90249a2f2.json"}}, {"family": "Jung", "given": "Bettina", "initials": "B"}, {"family": "Li", "given": "Yong", "initials": "Y"}, {"family": "Matias-Garcia", "given": "Pamela R", "initials": "PR"}, {"family": "Wuttke", "given": "Matthias", "initials": "M"}, {"family": "Coassin", "given": "Stefan", "initials": "S"}, {"family": "Thio", "given": "Chris H L", "initials": "CHL"}, {"family": "Kleber", "given": "Marcus E", "initials": "ME"}, {"family": "Winkler", "given": "Thomas W", "initials": "TW"}, {"family": "Wanner", "given": "Veronika", "initials": "V"}, {"family": "Chai", "given": "Jin-Fang", "initials": "J"}, {"family": "Chu", "given": "Audrey Y", "initials": "AY"}, {"family": "Cocca", "given": "Massimiliano", "initials": "M"}, {"family": "Feitosa", "given": "Mary F", "initials": "MF"}, {"family": "Ghasemi", "given": "Sahar", "initials": "S"}, {"family": "Hoppmann", "given": "Anselm", "initials": "A"}, {"family": "Horn", "given": "Katrin", "initials": "K"}, {"family": "Li", "given": "Man", "initials": "M"}, {"family": "Nutile", "given": "Teresa", "initials": "T"}, {"family": "Scholz", "given": "Markus", "initials": "M"}, {"family": "Sieber", "given": "Karsten B", "initials": "KB"}, {"family": "Teumer", "given": "Alexander", "initials": "A"}, {"family": "Tin", "given": "Adrienne", "initials": "A"}, {"family": "Wang", "given": "Judy", "initials": 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"Martin H", "initials": "MH"}, {"family": "Degenhardt", "given": "Frauke", "initials": "F"}, {"family": "Eckardt", "given": "Kai-Uwe", "initials": "K"}, {"family": "Endlich", "given": "Karlhans", "initials": "K"}, {"family": "Franke", "given": "Andre", "initials": "A"}, {"family": "Freitag-Wolf", "given": "Sandra", "initials": "S"}, {"family": "Gampawar", "given": "Piyush", "initials": "P"}, {"family": "Gansevoort", "given": "Ron T", "initials": "RT"}, {"family": "Ghanbari", "given": "Mohsen", "initials": "M"}, {"family": "Gieger", "given": "Christian", "initials": "C"}, {"family": "Hamet", "given": "Pavel", "initials": "P"}, {"family": "Ho", "given": "Kevin", "initials": "K"}, {"family": "Hofer", "given": "Edith", "initials": "E"}, {"family": "Holleczek", "given": "Bernd", "initials": "B"}, {"family": "Xian Foo", "given": "Valencia Hui", "initials": "VH"}, {"family": "Hutri-K\u00e4h\u00f6nen", "given": "Nina", "initials": "N"}, {"family": "Hwang", "given": "Shih-Jen", "initials": "S"}, {"family": "Ikram", "given": "M Arfan", "initials": "MA"}, {"family": "Josyula", "given": "Navya Shilpa", "initials": "NS"}, {"family": "K\u00e4h\u00f6nen", "given": "Mika", "initials": "M"}, {"family": "Khor", "given": "Chiea-Chuen", "initials": "C"}, {"family": "Koenig", "given": "Wolfgang", "initials": "W"}, {"family": "Kramer", "given": "Holly", "initials": "H"}, {"family": "Kr\u00e4mer", "given": "Bernhard K", "initials": "BK"}, {"family": "K\u00fchnel", "given": "Brigitte", "initials": "B"}, {"family": "Lange", "given": "Leslie A", "initials": "LA"}, {"family": "Lehtim\u00e4ki", "given": "Terho", "initials": "T"}, {"family": "Lieb", "given": "Wolfgang", "initials": "W"}, {"family": "Lifelines Cohort Study", "given": "", "initials": ""}, {"family": "Regeneron Genetics Center", "given": "", "initials": ""}, {"family": "Loos", "given": "Ruth J F", "initials": "RJF"}, {"family": "Lukas", "given": "Mary Ann", "initials": "MA"}, {"family": "Lyytik\u00e4inen", "given": "Leo-Pekka", "initials": "L"}, {"family": "Meisinger", "given": "Christa", "initials": "C"}, {"family": "Meitinger", "given": "Thomas", "initials": "T"}, {"family": "Melander", "given": "Olle", "initials": "O"}, {"family": "Milaneschi", "given": "Yuri", "initials": "Y"}, {"family": "Mishra", "given": "Pashupati P", "initials": "PP"}, {"family": "Mononen", "given": "Nina", "initials": "N"}, {"family": "Mychaleckyj", "given": "Josyf C", "initials": "JC"}, {"family": "Nadkarni", "given": "Girish N", "initials": "GN"}, {"family": "Nauck", "given": "Matthias", "initials": "M"}, {"family": "Nikus", "given": "Kjell", "initials": "K"}, {"family": "Ning", "given": "Boting", "initials": "B"}, {"family": "Nolte", "given": "Ilja M", "initials": "IM"}, {"family": "O'Donoghue", "given": "Michelle L", "initials": "ML"}, {"family": "Orho-Melander", "given": "Marju", "initials": "M"}, {"family": "Pendergrass", "given": "Sarah A", "initials": "SA"}, {"family": "Penninx", "given": "Brenda W J H", "initials": "BWJH"}, {"family": "Preuss", "given": "Michael H", "initials": "MH"}, {"family": "Psaty", "given": "Bruce M", "initials": "BM"}, {"family": "Raffield", "given": "Laura M", "initials": "LM"}, {"family": "Raitakari", "given": "Olli T", "initials": "OT"}, {"family": "Rettig", "given": "Rainer", "initials": "R"}, {"family": "Rheinberger", "given": "Myriam", "initials": "M"}, {"family": "Rice", "given": "Kenneth M", "initials": "KM"}, {"family": "Rosenkranz", "given": "Alexander R", "initials": "AR"}, {"family": "Rossing", "given": "Peter", "initials": "P"}, {"family": "Rotter", "given": "Jerome I", "initials": "JI"}, {"family": "Sabanayagam", "given": "Charumathi", "initials": "C"}, {"family": "Schmidt", "given": "Helena", "initials": "H"}, {"family": "Schmidt", "given": "Reinhold", "initials": "R"}, {"family": "Sch\u00f6ttker", "given": "Ben", "initials": "B"}, {"family": "Schulz", "given": "Christina-Alexandra", "initials": "C"}, {"family": "Sedaghat", "given": "Sanaz", "initials": "S"}, {"family": "Shaffer", "given": "Christian M", "initials": "CM"}, {"family": "Strauch", "given": "Konstantin", "initials": "K"}, {"family": "Szymczak", "given": "Silke", "initials": "S"}, {"family": "Taylor", "given": "Kent D", "initials": "KD"}, {"family": "Tremblay", "given": "Johanne", "initials": "J"}, {"family": "Chaker", "given": "Layal", "initials": "L"}, {"family": "van der Harst", "given": "Pim", "initials": "P"}, {"family": "van der Most", "given": "Peter J", "initials": "PJ"}, {"family": "Verweij", "given": "Niek", "initials": "N"}, {"family": "V\u00f6lker", "given": "Uwe", "initials": "U"}, {"family": "Waldenberger", "given": "Melanie", "initials": "M"}, {"family": "Wallentin", "given": "Lars", "initials": "L"}, {"family": "Waterworth", "given": "Dawn M", "initials": "DM"}, {"family": "White", "given": "Harvey D", "initials": "HD"}, {"family": "Wilson", "given": "James G", "initials": "JG"}, {"family": "Wong", "given": "Tien-Yin", "initials": "T"}, {"family": "Woodward", "given": "Mark", "initials": "M"}, {"family": "Yang", "given": "Qiong", "initials": "Q"}, {"family": "Yasuda", "given": "Masayuki", "initials": "M"}, {"family": "Yerges-Armstrong", "given": "Laura M", "initials": "LM"}, {"family": "Zhang", "given": "Yan", "initials": "Y"}, {"family": "Snieder", "given": "Harold", "initials": "H"}, {"family": "Wanner", "given": "Christoph", "initials": "C"}, {"family": "B\u00f6ger", "given": "Carsten A", "initials": "CA"}, {"family": "K\u00f6ttgen", "given": "Anna", "initials": "A", "orcid": "0000-0002-4671-3714", "researcher": {"href": "https://publications.scilifelab.se/researcher/fe4cb85a14da4db6bc932a8bc4148efb.json"}}, {"family": "Kronenberg", "given": "Florian", "initials": "F"}, {"family": "Pattaro", "given": "Cristian", "initials": "C"}, {"family": "Heid", "given": "Iris M", "initials": "IM"}], "type": "journal article", "published": "2021-04-00", "journal": {"title": "Kidney Int.", "issn": "1523-1755", "issn-l": "0085-2538", "volume": "99", "issue": "4", "pages": "926-939"}, "abstract": "Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m2/year or more (\"Rapid3\"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m2 at follow-up among those with eGFRcrea 60 mL/min/1.73m2 or more at baseline (\"CKDi25\"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or LARP4B. Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.", "doi": "10.1016/j.kint.2020.09.030", "pmid": "33137338", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "S0085-2538(20)31239-4"}, {"db": "pmc", "key": "PMC8010357"}, {"db": "mid", "key": "NIHMS1677067"}], "notes": [], "created": "2020-11-05T14:07:50.074Z", "modified": "2021-12-07T13:33:16.249Z"}