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{"family": "Tobias", "given": "Jonathan H", "initials": "JH"}, {"family": "Ohlsson", "given": "Claes", "initials": "C", "orcid": "0000-0002-9633-2805", "researcher": {"href": "https://publications.scilifelab.se/researcher/995dac358caa4a169fc889b7a3eef44a.json"}}, {"family": "Felix", "given": "Janine F", "initials": "JF", "orcid": "0000-0002-9801-5774", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a4482378cb24a9f832729f7004a41bf.json"}}, {"family": "Bisgaard", "given": "Hans", "initials": "H"}, {"family": "Grant", "given": "Struan F A", "initials": "SFA"}, {"family": "Richards", "given": "J Brent", "initials": "JB", "orcid": "0000-0002-3746-9086", "researcher": {"href": "https://publications.scilifelab.se/researcher/c2c20c901fd041c194dae79b29b94ec2.json"}}, {"family": "Evans", "given": "David M", "initials": "DM", "orcid": "0000-0003-0663-4621", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b9b78a6c5b94bf18b798318935f62fd.json"}}, {"family": "van der Eerden", "given": "Bram", "initials": "B", "orcid": "0000-0003-4403-6497", "researcher": {"href": "https://publications.scilifelab.se/researcher/42514d51463941c5aad5083d181f0fe2.json"}}, {"family": "van de Peppel", "given": "Jeroen", "initials": "J"}, {"family": "Ackert-Bicknell", "given": "Cheryl", "initials": "C", "orcid": "0000-0003-4253-4775", "researcher": {"href": "https://publications.scilifelab.se/researcher/c843d9e827da46be81741184b57a4e38.json"}}, {"family": "Karasik", "given": "David", "initials": "D", "orcid": "0000-0002-8826-0530", "researcher": {"href": "https://publications.scilifelab.se/researcher/309cc98072424c52a29438620f03bfa0.json"}}, {"family": "Kague", "given": "Erika", "initials": "E", "orcid": "0000-0002-0266-9424", "researcher": {"href": "https://publications.scilifelab.se/researcher/cde5eaa107d04bb494e2567e66d75f71.json"}}, {"family": "Rivadeneira", "given": "Fernando", "initials": "F", "orcid": "0000-0001-9435-9441", "researcher": {"href": "https://publications.scilifelab.se/researcher/f8894904d3cf4671a2e563169829322a.json"}}], "type": "meta-analysis", "published": "2023-07-04", "journal": {"title": "Commun Biol", "issn": "2399-3642", "issn-l": "2399-3642", "volume": "6", "issue": "1", "pages": "691"}, "abstract": "Skull bone mineral density (SK-BMD) provides a suitable trait for the discovery of key genes in bone biology, particularly to intramembranous ossification, not captured at other skeletal sites. We perform a genome-wide association meta-analysis (n ~ 43,800) of SK-BMD, identifying 59 loci, collectively explaining 12.5% of the trait variance. Association signals cluster within gene-sets involved in skeletal development and osteoporosis. Among the four novel loci (ZIC1, PRKAR1A, AZIN1/ATP6V1C1, GLRX3), there are factors implicated in intramembranous ossification and as we show, inherent to craniosynostosis processes. Functional follow-up in zebrafish confirms the importance of ZIC1 on cranial suture patterning. Likewise, we observe abnormal cranial bone initiation that culminates in ectopic sutures and reduced BMD in mosaic atp6v1c1 knockouts. Mosaic prkar1a knockouts present asymmetric bone growth and, conversely, elevated BMD. In light of this evidence linking SK-BMD loci to craniofacial abnormalities, our study provides new insight into the pathophysiology, diagnosis and treatment of skeletal diseases.", "doi": "10.1038/s42003-023-04869-0", "pmid": "37402774", "labels": {"Clinical Genomics Gothenburg": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC10319806"}, {"db": "pii", "key": "10.1038/s42003-023-04869-0"}], "notes": [], "created": "2023-11-30T22:35:09.520Z", "modified": "2023-11-30T22:36:33.714Z"}, {"entity": "publication", "iuid": "20044ca7f045473daf17863e0344b451", "links": {"self": {"href": "https://publications.scilifelab.se/publication/20044ca7f045473daf17863e0344b451.json"}, "display": {"href": "https://publications.scilifelab.se/publication/20044ca7f045473daf17863e0344b451"}}, "title": "Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals.", "authors": [{"family": "Winkler", "given": "Thomas W", "initials": "TW", "orcid": "0000-0003-0292-5421", "researcher": {"href": "https://publications.scilifelab.se/researcher/613c02e5736a4357bcfff184bebb714e.json"}}, {"family": "Rasheed", "given": "Humaira", "initials": "H", "orcid": "0000-0002-3331-5864", "researcher": {"href": "https://publications.scilifelab.se/researcher/bfbae7ea55074f9292e48aaf6d815a03.json"}}, {"family": "Teumer", "given": "Alexander", "initials": "A", "orcid": "0000-0002-8309-094X", "researcher": {"href": "https://publications.scilifelab.se/researcher/dc9c2667a55b47a6a08aea764fab0946.json"}}, {"family": "Gorski", "given": "Mathias", "initials": "M"}, {"family": "Rowan", "given": "Bryce X", "initials": "BX"}, {"family": "Stanzick", "given": "Kira J", "initials": "KJ"}, {"family": "Thomas", "given": "Laurent F", "initials": "LF"}, {"family": "Tin", "given": "Adrienne", "initials": "A", "orcid": "0000-0002-4207-5866", "researcher": {"href": 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"https://publications.scilifelab.se/researcher/679465193fba4887a68e2aec34ccfd8e.json"}}, {"family": "B\u00f6ger", "given": "Carsten A", "initials": "CA"}, {"family": "Hung", "given": "Adriana M", "initials": "AM"}, {"family": "Kronenberg", "given": "Florian", "initials": "F", "orcid": "0000-0003-2229-1120", "researcher": {"href": "https://publications.scilifelab.se/researcher/ebc59079554842ecb3512ef90249a2f2.json"}}, {"family": "K\u00f6ttgen", "given": "Anna", "initials": "A", "orcid": "0000-0002-4671-3714", "researcher": {"href": "https://publications.scilifelab.se/researcher/fe4cb85a14da4db6bc932a8bc4148efb.json"}}, {"family": "Pattaro", "given": "Cristian", "initials": "C", "orcid": "0000-0002-4119-0109", "researcher": {"href": "https://publications.scilifelab.se/researcher/3a6a570bbec647b188c4a7a5da03caac.json"}}, {"family": "Heid", "given": "Iris M", "initials": "IM", "orcid": "0000-0002-4122-5308", "researcher": {"href": "https://publications.scilifelab.se/researcher/34990140a9604dd7b61807dafc8fabc6.json"}}], "type": "journal article", "published": "2022-06-13", "journal": {"title": "Commun Biol", "issn": "2399-3642", "volume": "5", "issue": "1", "pages": "580", "issn-l": "2399-3642"}, "abstract": "Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (nDM = 178,691, nnoDM = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.", "doi": "10.1038/s42003-022-03448-z", "pmid": "35697829", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "NGI SNP genotyping": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s42003-022-03448-z"}, {"db": "pmc", "key": "PMC9192715"}], "notes": [], "created": "2022-06-14T13:16:22.813Z", "modified": "2022-11-21T15:40:40.440Z"}, {"entity": "publication", "iuid": "43bc6c3af57d4f21b3b55ea14d7b176a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/43bc6c3af57d4f21b3b55ea14d7b176a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/43bc6c3af57d4f21b3b55ea14d7b176a"}}, "title": "An ARHGAP25 variant links aberrant Rac1 function to early-onset skeletal fragility.", "authors": [{"family": "M\u00e4kitie", "given": "Riikka E", "initials": "RE", "orcid": "0000-0002-2907-3348", "researcher": {"href": "https://publications.scilifelab.se/researcher/4473e684b3e943be942d4603a0705c41.json"}}, {"family": "Henning", "given": "Petra", "initials": "P"}, {"family": "Jiu", "given": "Yaming", "initials": "Y"}, {"family": "K\u00e4mpe", "given": "Anders", "initials": "A", "orcid": "0000-0002-1829-3855", "researcher": {"href": "https://publications.scilifelab.se/researcher/0785e17b57384962a0ff9bc7ecaa80c8.json"}}, {"family": "Kogan", "given": "Konstantin", "initials": "K"}, {"family": "Costantini", "given": "Alice", "initials": "A", "orcid": "0000-0003-1408-9272", "researcher": {"href": "https://publications.scilifelab.se/researcher/1d1ec6874e0c41b8a22cb4c0f3275bec.json"}}, {"family": "V\u00e4lim\u00e4ki", "given": "Ville-Valtteri", "initials": "VV"}, {"family": "Medina-Gomez", "given": "Carolina", "initials": "C"}, {"family": "Pekkinen", "given": "Minna", "initials": "M"}, {"family": "Salusky", "given": "Isidro B", "initials": "IB"}, {"family": "Schalin-J\u00e4ntti", "given": "Camilla", "initials": "C", "orcid": "0000-0002-2428-0161", "researcher": {"href": "https://publications.scilifelab.se/researcher/68115a9a6e2a400a82508dc5bec652fd.json"}}, {"family": "Haanp\u00e4\u00e4", "given": "Maria K", "initials": "MK"}, {"family": "Rivadeneira", "given": "Fernando", "initials": "F", "orcid": "0000-0001-9435-9441", "researcher": {"href": "https://publications.scilifelab.se/researcher/f8894904d3cf4671a2e563169829322a.json"}}, {"family": "Bassett", "given": "John H Duncan", "initials": "JHD", "orcid": "0000-0003-0817-0082", "researcher": {"href": "https://publications.scilifelab.se/researcher/44156a0ff8df49cab6a99cf75b26374f.json"}}, {"family": "Williams", "given": "Graham R", "initials": "GR", "orcid": "0000-0002-8555-8219", "researcher": {"href": "https://publications.scilifelab.se/researcher/2ac4b0d0862b4bae8fa1cf3323c74f92.json"}}, {"family": "Lerner", "given": "Ulf H", "initials": "UH"}, {"family": "Pereira", "given": "Renata C", "initials": "RC"}, {"family": "Lappalainen", "given": "Pekka", "initials": "P"}, {"family": "M\u00e4kitie", "given": "Outi", "initials": "O", "orcid": "0000-0002-4547-001X", "researcher": {"href": "https://publications.scilifelab.se/researcher/ce0614bdc717455b9af64a05ab4aa4aa.json"}}], "type": "journal article", "published": "2021-07-00", "journal": {"title": "JBMR Plus", "issn": "2473-4039", "volume": "5", "issue": "7", "pages": "e10509", "issn-l": null}, "abstract": "Ras homologous guanosine triphosphatases (RhoGTPases) control several cellular functions, including cytoskeletal actin remodeling and cell migration. Their activities are downregulated by GTPase-activating proteins (GAPs). Although RhoGTPases are implicated in bone remodeling and osteoclast and osteoblast function, their significance in human bone health and disease remains elusive. Here, we report defective RhoGTPase regulation as a cause of severe, early-onset, autosomal-dominant skeletal fragility in a three-generation Finnish family. Affected individuals (n = 13) presented with multiple low-energy peripheral and vertebral fractures despite normal bone mineral density (BMD). Bone histomorphometry suggested reduced bone volume, low surface area covered by osteoblasts and osteoclasts, and low bone turnover. Exome sequencing identified a novel heterozygous missense variant c.652G>A (p.G218R) in ARHGAP25, encoding a GAP for Rho-family GTPase Rac1. Variants in the ARHGAP25 5' untranslated region (UTR) also associated with BMD and fracture risk in the general population, across multiple genomewide association study (GWAS) meta-analyses (lead variant rs10048745). ARHGAP25 messenger RNA (mRNA) was expressed in macrophage colony-stimulating factor (M-CSF)-stimulated human monocytes and mouse osteoblasts, indicating a possible role for ARHGAP25 in osteoclast and osteoblast differentiation and activity. Studies on subject-derived osteoclasts from peripheral blood mononuclear cells did not reveal robust defects in mature osteoclast formation or resorptive activity. However, analysis of osteosarcoma cells overexpressing the ARHGAP25 G218R-mutant, combined with structural modeling, confirmed that the mutant protein had decreased GAP-activity against Rac1, resulting in elevated Rac1 activity, increased cell spreading, and membrane ruffling. Our findings indicate that mutated ARHGAP25 causes aberrant Rac1 function and consequently abnormal bone metabolism, highlighting the importance of RhoGAP signaling in bone metabolism in familial forms of skeletal fragility and in the general population, and expanding our understanding of the molecular pathways underlying skeletal fragility. \u00a9 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.", "doi": "10.1002/jbm4.10509", "pmid": "34258505", "labels": {"Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "JBM410509"}, {"db": "pmc", "key": "PMC8260816"}], "notes": [], "created": "2022-11-09T15:55:53.681Z", "modified": "2024-01-16T13:48:39.379Z"}, {"entity": "publication", "iuid": "89c87476555544e39ef6bf6717603f84", "links": {"self": {"href": "https://publications.scilifelab.se/publication/89c87476555544e39ef6bf6717603f84.json"}, "display": {"href": "https://publications.scilifelab.se/publication/89c87476555544e39ef6bf6717603f84"}}, "title": "Associations of autozygosity with a broad range of human phenotypes.", "authors": [{"family": "Clark", "given": "David W", "initials": "DW", "orcid": "0000-0002-1025-9185", "researcher": {"href": "https://publications.scilifelab.se/researcher/a71ee9badf4f458d9b04ebf89f5f16c9.json"}}, {"family": "Okada", "given": "Yukinori", "initials": "Y", "orcid": "0000-0002-0311-8472", "researcher": {"href": "https://publications.scilifelab.se/researcher/40b13860bfef41959c29be2de853b456.json"}}, {"family": "Moore", "given": "Kristjan H S", "initials": "KHS", "orcid": "0000-0002-9579-4362", "researcher": {"href": "https://publications.scilifelab.se/researcher/38a8eaf6f23c4dd9a90cda85b0a998b5.json"}}, {"family": "Mason", "given": "Dan", "initials": "D", "orcid": "0000-0002-0026-9216", "researcher": {"href": "https://publications.scilifelab.se/researcher/3e9d969adc0849ab83d0080430bb6758.json"}}, {"family": "Pirastu", "given": "Nicola", "initials": "N", "orcid": "0000-0002-5363-3886", "researcher": {"href": "https://publications.scilifelab.se/researcher/badf4678d37546ce993bccb3880d4f12.json"}}, {"family": "Gandin", "given": "Ilaria", "initials": "I", "orcid": "0000-0003-3196-2491", "researcher": {"href": 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"initials": "F", "orcid": "0000-0001-9435-9441", "researcher": {"href": "https://publications.scilifelab.se/researcher/f8894904d3cf4671a2e563169829322a.json"}}, {"family": "Rotimi", "given": "Charles", "initials": "C", "orcid": "0000-0001-5759-053X", "researcher": {"href": "https://publications.scilifelab.se/researcher/7fa2951fdebf4fddaad296d49b8f3f2b.json"}}, {"family": "Rotter", "given": "Jerome I", "initials": "JI", "orcid": "0000-0001-7191-1723", "researcher": {"href": "https://publications.scilifelab.se/researcher/7e9bdbf58ae94fc8b455bbbcbcaa50ce.json"}}, {"family": "Rudan", "given": "Igor", "initials": "I", "orcid": "0000-0001-6993-6884", "researcher": {"href": "https://publications.scilifelab.se/researcher/d50e1ca836e841f8a7a748ae93b59d75.json"}}, {"family": "Den Ruijter", "given": "Hester M", "initials": "HM"}, {"family": "Sanghera", "given": "Dharambir K", "initials": "DK"}, {"family": "Sattar", "given": "Naveed", "initials": "N", "orcid": "0000-0002-1604-2593", "researcher": {"href": "https://publications.scilifelab.se/researcher/80fbc7cdcfc444acb066449f80f87181.json"}}, {"family": "Schmidt", "given": "Reinhold", "initials": "R"}, {"family": "Schulze", "given": "Matthias B", "initials": "MB"}, {"family": "Schunkert", "given": "Heribert", "initials": "H"}, {"family": "Scott", "given": "Robert A", "initials": "RA"}, {"family": "Shuldiner", "given": "Alan R", "initials": "AR"}, {"family": "Sim", "given": "Xueling", "initials": "X", "orcid": "0000-0002-1233-7642", "researcher": {"href": "https://publications.scilifelab.se/researcher/3216a8d2a7264a1390a886fa09d5d648.json"}}, {"family": "Small", "given": "Neil", "initials": "N"}, {"family": "Smith", "given": "Jennifer A", "initials": "JA", "orcid": "0000-0002-3575-5468", "researcher": {"href": "https://publications.scilifelab.se/researcher/311c7381092b4143bcd2e4ef93250526.json"}}, {"family": "Sotoodehnia", "given": "Nona", "initials": "N"}, {"family": "Tai", "given": "E-Shyong", "initials": "ES"}, {"family": "Teumer", "given": "Alexander", "initials": "A", "orcid": "0000-0002-8309-094X", "researcher": {"href": "https://publications.scilifelab.se/researcher/dc9c2667a55b47a6a08aea764fab0946.json"}}, {"family": "Timpson", "given": "Nicholas J", "initials": "NJ", "orcid": "0000-0002-7141-9189", "researcher": {"href": "https://publications.scilifelab.se/researcher/764ab7a82db24557a5de0fad97bf53f3.json"}}, {"family": "Toniolo", "given": "Daniela", "initials": "D"}, {"family": "Tregouet", "given": "David-Alexandre", "initials": "DA"}, {"family": "Tuomi", "given": "Tiinamaija", "initials": "T", "orcid": "0000-0002-8306-6202", "researcher": {"href": "https://publications.scilifelab.se/researcher/19f5ce9936ca454c85f0af966acac5c0.json"}}, {"family": "Vollenweider", "given": "Peter", "initials": "P"}, {"family": "Wang", "given": "Carol A", "initials": "CA", "orcid": "0000-0002-4301-3974", "researcher": {"href": "https://publications.scilifelab.se/researcher/bf99a43c27034a68976e978b104a91d7.json"}}, {"family": "Weir", "given": "David R", "initials": "DR", "orcid": "0000-0002-1661-2402", "researcher": {"href": "https://publications.scilifelab.se/researcher/f90b7cfe829845fb8cbea9558a5c82a7.json"}}, {"family": "Whitfield", "given": "John B", "initials": "JB", "orcid": "0000-0002-1103-0876", "researcher": {"href": "https://publications.scilifelab.se/researcher/e0f61a914f9748ee9047301da8026bd7.json"}}, {"family": "Wijmenga", "given": "Cisca", "initials": "C"}, {"family": "Wong", "given": "Tien-Yin", "initials": "TY"}, {"family": "Wright", "given": "John", "initials": "J"}, {"family": "Yang", "given": "Jingyun", "initials": "J"}, {"family": "Yu", "given": "Lei", "initials": "L"}, {"family": "Zemel", "given": "Babette S", "initials": "BS"}, {"family": "Zonderman", "given": "Alan B", "initials": "AB"}, {"family": "Perola", "given": "Markus", "initials": "M"}, {"family": "Magnusson", "given": "Patrik K E", "initials": "PKE", "orcid": "0000-0002-7315-7899", "researcher": {"href": "https://publications.scilifelab.se/researcher/b277b6387de142bbab91fad82d9eff09.json"}}, {"family": "Uitterlinden", "given": "Andr\u00e9 G", "initials": "AG", "orcid": "0000-0002-7276-3387", "researcher": {"href": "https://publications.scilifelab.se/researcher/273577b238854023a9dffe34dabc3551.json"}}, {"family": "Kooner", "given": "Jaspal S", "initials": "JS"}, {"family": "Chasman", "given": "Daniel I", "initials": "DI"}, {"family": "Loos", "given": "Ruth J F", "initials": "RJF", "orcid": "0000-0002-8532-5087", "researcher": {"href": "https://publications.scilifelab.se/researcher/e5b6c24c302d42828806076ded81afe1.json"}}, {"family": "Franceschini", "given": "Nora", "initials": "N"}, {"family": "Franke", "given": "Lude", "initials": "L", "orcid": "0000-0002-5159-8802", "researcher": {"href": "https://publications.scilifelab.se/researcher/ee63161f78274a53b615c05555b81a10.json"}}, {"family": "Haley", "given": "Chris S", "initials": "CS", "orcid": "0000-0002-9811-0210", "researcher": {"href": "https://publications.scilifelab.se/researcher/c4fee769cfe84186abbc285881e0529c.json"}}, {"family": "Hayward", "given": "Caroline", "initials": "C", "orcid": "0000-0002-9405-9550", "researcher": {"href": "https://publications.scilifelab.se/researcher/cd49e9ad5a024c7ca2f1aa97d9e58eba.json"}}, {"family": "Walters", "given": "Robin G", "initials": "RG", "orcid": "0000-0002-9179-0321", "researcher": {"href": "https://publications.scilifelab.se/researcher/f36254611faa44b782b76da870e89bd3.json"}}, {"family": "Perry", "given": "John R B", "initials": "JRB"}, {"family": "Esko", "given": "T\u014dnu", "initials": "T"}, {"family": "Helgason", "given": "Agnar", "initials": "A"}, {"family": "Stefansson", "given": "Kari", "initials": "K"}, {"family": "Joshi", "given": "Peter K", "initials": "PK", "orcid": "0000-0002-6361-5059", "researcher": {"href": "https://publications.scilifelab.se/researcher/46050ddec8f64054b3bab46c5016aebf.json"}}, {"family": "Kubo", "given": "Michiaki", "initials": "M"}, {"family": "Wilson", "given": "James F", "initials": "JF", "orcid": "0000-0001-5751-9178", "researcher": {"href": "https://publications.scilifelab.se/researcher/b39e6e0f7210494cb4f80be0f7413b6f.json"}}], "type": "journal article", "published": "2019-10-31", "journal": {"volume": "10", "issn": "2041-1723", "issue": "1", "pages": "4957", "title": "Nat Commun", "issn-l": "2041-1723"}, "abstract": "In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.", "doi": "10.1038/s41467-019-12283-6", "pmid": "31673082", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC6823371"}, {"db": "pii", "key": "10.1038/s41467-019-12283-6"}], "notes": [], "created": "2019-11-28T07:41:34.797Z", "modified": "2023-06-19T13:09:10.356Z"}, {"entity": "publication", "iuid": "a212f36b24ed408086fd6d1b5ab1eab5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a212f36b24ed408086fd6d1b5ab1eab5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a212f36b24ed408086fd6d1b5ab1eab5"}}, "title": "A catalog of genetic loci associated with kidney function from analyses of a million individuals.", "authors": [{"family": "Wuttke", "given": "Matthias", "initials": "M", "orcid": 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"https://publications.scilifelab.se/researcher/df3f5b6e8cb7470c880cff6dc960f283.json"}}, {"family": "Heid", "given": "Iris M", "initials": "IM"}, {"family": "Scholz", "given": "Markus", "initials": "M", "orcid": "0000-0002-4059-1779", "researcher": {"href": "https://publications.scilifelab.se/researcher/53d7b0e2dcdb4361b54016cb1550c5fe.json"}}, {"family": "Teumer", "given": "Alexander", "initials": "A", "orcid": "0000-0002-8309-094X", "researcher": {"href": "https://publications.scilifelab.se/researcher/dc9c2667a55b47a6a08aea764fab0946.json"}}, {"family": "K\u00f6ttgen", "given": "Anna", "initials": "A", "orcid": "0000-0002-4671-3714", "researcher": {"href": "https://publications.scilifelab.se/researcher/fe4cb85a14da4db6bc932a8bc4148efb.json"}}, {"family": "Pattaro", "given": "Cristian", "initials": "C", "orcid": "0000-0002-4119-0109", "researcher": {"href": "https://publications.scilifelab.se/researcher/3a6a570bbec647b188c4a7a5da03caac.json"}}], "type": "journal article", "published": "2019-06-00", "journal": {"volume": "51", "issn": "1546-1718", "issue": "6", "pages": "957-972", "title": "Nat. Genet.", "issn-l": "1061-4036"}, "abstract": "Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.", "doi": "10.1038/s41588-019-0407-x", "pmid": "31152163", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41588-019-0407-x"}, {"db": "pmc", "key": "PMC6698888"}, {"db": "mid", "key": "NIHMS1038587"}], "notes": [], "created": "2019-06-04T12:49:02.356Z", "modified": "2021-06-21T11:50:41.587Z"}]}