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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": "08350a98d5d042829c1d154c715361d9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/08350a98d5d042829c1d154c715361d9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/08350a98d5d042829c1d154c715361d9"}}, "title": "Epigenome-wide association study of serum urate reveals insights into urate co-regulation and the SLC2A9 locus.", "authors": [{"family": "Tin", "given": "Adrienne", "initials": "A", "orcid": "0000-0002-4207-5866", "researcher": {"href": "https://publications.scilifelab.se/researcher/b9c33ed3b64348be904a14698402445e.json"}}, {"family": "Schlosser", "given": "Pascal", "initials": "P", "orcid": "0000-0002-8460-0462", "researcher": {"href": "https://publications.scilifelab.se/researcher/b69be66d160c4cdc8030a07ebcb8f150.json"}}, {"family": "Matias-Garcia", "given": "Pamela R", "initials": "PR"}, {"family": "Thio", "given": "Chris H L", "initials": "CHL", "orcid": "0000-0003-2623-7172", "researcher": {"href": "https://publications.scilifelab.se/researcher/47fba5312ce6449fb9cfc45f6e1717e1.json"}}, {"family": "Joehanes", "given": "Roby", "initials": "R"}, {"family": "Liu", "given": "Hongbo", "initials": "H", "orcid": "0000-0002-0733-8616", "researcher": {"href": "https://publications.scilifelab.se/researcher/ed1bef0b625f42249a5f5364e3759e71.json"}}, {"family": "Yu", "given": "Zhi", "initials": "Z", "orcid": "0000-0003-4810-3474", "researcher": {"href": 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"initials": "S"}, {"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": "Stocker", "given": "Hannah R", "initials": "HR", "orcid": "0000-0001-5281-2455", "researcher": {"href": "https://publications.scilifelab.se/researcher/1b29536e37004e708b1c75abc369d1f2.json"}}, {"family": "Stringhini", "given": "Silvia", "initials": "S", "orcid": "0000-0002-4387-8943", "researcher": {"href": "https://publications.scilifelab.se/researcher/e670989692024cc581612a876237d6a7.json"}}, {"family": "Sundstr\u00f6m", "given": "Johan", "initials": "J", "orcid": "0000-0003-2247-8454", "researcher": {"href": "https://publications.scilifelab.se/researcher/91a40d3c138d43f2b0d38f66be4b71c7.json"}}, {"family": "Swenson", "given": "Brenton R", "initials": "BR"}, {"family": "van Meurs", "given": "Joyce B J", "initials": "JBJ"}, {"family": "van Vliet-Ostaptchouk", "given": "Jana V", "initials": "JV", "orcid": "0000-0002-7943-3153", "researcher": {"href": "https://publications.scilifelab.se/researcher/babcbf8d8f124eceaf0a06dffd39b5cb.json"}}, {"family": "Venema", "given": "Andrea", "initials": "A"}, {"family": "V\u00f6lker", "given": "Uwe", "initials": "U", "orcid": "0000-0002-5689-3448", "researcher": {"href": "https://publications.scilifelab.se/researcher/e529a40052644d83bdef588a3e4f4e99.json"}}, {"family": "Winkelmann", "given": "Juliane", "initials": "J"}, {"family": "Wolffenbuttel", "given": "Bruce H R", "initials": "BHR", "orcid": "0000-0001-9262-6921", "researcher": {"href": "https://publications.scilifelab.se/researcher/705d5bb109c443289feef937e695dc7d.json"}}, {"family": "Zhao", "given": "Wei", "initials": "W", "orcid": "0000-0001-7388-0692", "researcher": {"href": "https://publications.scilifelab.se/researcher/a0c2246e69494086bab7ead8e6f1f717.json"}}, {"family": "Zheng", "given": "Yinan", "initials": "Y", "orcid": "0000-0002-2006-7320", "researcher": {"href": "https://publications.scilifelab.se/researcher/dd8f1e7f80ee4aa8b853ef31295f5709.json"}}, {"family": "Estonian Biobank Research Team", "given": "", "initials": ""}, {"family": "Genetics of DNA Methylation Consortium", "given": "", "initials": ""}, {"family": "Loh", "given": "Marie", "initials": "M", "orcid": "0000-0003-3626-8466", "researcher": {"href": "https://publications.scilifelab.se/researcher/70e1d986dce444f889fda8d47e9cb355.json"}}, {"family": "Snieder", "given": "Harold", "initials": "H", "orcid": "0000-0003-1949-2298", "researcher": {"href": "https://publications.scilifelab.se/researcher/e9276827839a4f3cb50dcaa2ad4708a5.json"}}, {"family": "Waldenberger", "given": "Melanie", "initials": "M", "orcid": "0000-0003-0583-5093", "researcher": {"href": "https://publications.scilifelab.se/researcher/c8de22214f2448c6a7f86fc1040d0104.json"}}, {"family": "Levy", "given": "Daniel", "initials": "D", "orcid": "0000-0003-1843-8724", "researcher": {"href": "https://publications.scilifelab.se/researcher/86bfd3e65ead428c93dc1a461004adab.json"}}, {"family": "Akilesh", "given": "Shreeram", "initials": "S", "orcid": "0000-0003-3152-7991", "researcher": {"href": "https://publications.scilifelab.se/researcher/1cb143e90633471486dbad753d06e3fe.json"}}, {"family": "Woodward", "given": "Owen M", "initials": "OM", "orcid": "0000-0001-9514-2180", "researcher": {"href": "https://publications.scilifelab.se/researcher/669278c697764d249d6668a7d59269a6.json"}}, {"family": "Susztak", "given": "Katalin", "initials": "K", "orcid": "0000-0002-1005-3726", "researcher": {"href": "https://publications.scilifelab.se/researcher/1382eacb5f28444396132254487e3ed9.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"}}], "type": "journal article", "published": "2021-12-09", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "12", "issue": "1", "pages": "7173", "issn-l": "2041-1723"}, "abstract": "Elevated serum urate levels, a complex trait and major risk factor for incident gout, are correlated with cardiometabolic traits via incompletely understood mechanisms. DNA methylation in whole blood captures genetic and environmental influences and is assessed in transethnic meta-analysis of epigenome-wide association studies (EWAS) of serum urate (discovery, n = 12,474, replication, n = 5522). The 100 replicated, epigenome-wide significant (p < 1.1E-7) CpGs explain 11.6% of the serum urate variance. At SLC2A9, the serum urate locus with the largest effect in genome-wide association studies (GWAS), five CpGs are associated with SLC2A9 gene expression. Four CpGs at SLC2A9 have significant causal effects on serum urate levels and/or gout, and two of these partly mediate the effects of urate-associated GWAS variants. In other genes, including SLC7A11 and PHGDH, 17 urate-associated CpGs are associated with conditions defining metabolic syndrome, suggesting that these CpGs may represent a blood DNA methylation signature of cardiometabolic risk factors. This study demonstrates that EWAS can provide new insights into GWAS loci and the correlation of serum urate with other complex traits.", "doi": "10.1038/s41467-021-27198-4", "pmid": "34887389", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-021-27198-4"}], "notes": [], "created": "2021-12-22T19:39:57.979Z", "modified": "2021-12-22T19:39:58.563Z"}, {"entity": "publication", "iuid": "c6fcde1c149146be8ea0b5308f8ec628", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c6fcde1c149146be8ea0b5308f8ec628.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c6fcde1c149146be8ea0b5308f8ec628"}}, "title": "Meta-analyses identify DNA methylation associated with kidney function and damage.", "authors": [{"family": "Schlosser", "given": "Pascal", "initials": "P", "orcid": "0000-0002-8460-0462", "researcher": {"href": 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"Niek", "initials": "N"}, {"family": "Walker", "given": "Rosie M", "initials": "RM", "orcid": "0000-0002-1060-4479", "researcher": {"href": "https://publications.scilifelab.se/researcher/79a65025d1a64ed2b383e69c803df0a4.json"}}, {"family": "Wielscher", "given": "Matthias", "initials": "M", "orcid": "0000-0003-4138-1383", "researcher": {"href": "https://publications.scilifelab.se/researcher/18bdf16f6b9f4272ae4b03579dc46e00.json"}}, {"family": "Winkelmann", "given": "Juliane", "initials": "J"}, {"family": "Wolffenbuttel", "given": "Bruce H R", "initials": "BHR", "orcid": "0000-0001-9262-6921", "researcher": {"href": "https://publications.scilifelab.se/researcher/705d5bb109c443289feef937e695dc7d.json"}}, {"family": "Zhao", "given": "Wei", "initials": "W", "orcid": "0000-0001-7388-0692", "researcher": {"href": "https://publications.scilifelab.se/researcher/a0c2246e69494086bab7ead8e6f1f717.json"}}, {"family": "Zheng", "given": "Yinan", "initials": "Y", "orcid": "0000-0002-2006-7320", "researcher": {"href": "https://publications.scilifelab.se/researcher/dd8f1e7f80ee4aa8b853ef31295f5709.json"}}, {"family": "Estonian Biobank Research Team", "given": "", "initials": ""}, {"family": "Genetics of DNA Methylation Consortium", "given": "", "initials": ""}, {"family": "Loh", "given": "Marie", "initials": "M", "orcid": "0000-0003-3626-8466", "researcher": {"href": "https://publications.scilifelab.se/researcher/70e1d986dce444f889fda8d47e9cb355.json"}}, {"family": "Snieder", "given": "Harold", "initials": "H", "orcid": "0000-0003-1949-2298", "researcher": {"href": "https://publications.scilifelab.se/researcher/e9276827839a4f3cb50dcaa2ad4708a5.json"}}, {"family": "Levy", "given": "Daniel", "initials": "D", "orcid": "0000-0003-1843-8724", "researcher": {"href": "https://publications.scilifelab.se/researcher/86bfd3e65ead428c93dc1a461004adab.json"}}, {"family": "Waldenberger", "given": "Melanie", "initials": "M", "orcid": "0000-0003-0583-5093", "researcher": {"href": "https://publications.scilifelab.se/researcher/c8de22214f2448c6a7f86fc1040d0104.json"}}, {"family": "Susztak", "given": "Katalin", "initials": "K", "orcid": "0000-0002-1005-3726", "researcher": {"href": "https://publications.scilifelab.se/researcher/1382eacb5f28444396132254487e3ed9.json"}}, {"family": "K\u00f6ttgen", "given": "Anna", "initials": "A", "orcid": "0000-0002-4671-3714", "researcher": {"href": "https://publications.scilifelab.se/researcher/fe4cb85a14da4db6bc932a8bc4148efb.json"}}, {"family": "Teumer", "given": "Alexander", "initials": "A", "orcid": "0000-0002-8309-094X", "researcher": {"href": "https://publications.scilifelab.se/researcher/dc9c2667a55b47a6a08aea764fab0946.json"}}], "type": "journal article", "published": "2021-12-09", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "12", "issue": "1", "pages": "7174", "issn-l": "2041-1723"}, "abstract": "Chronic kidney disease is a major public health burden. Elevated urinary albumin-to-creatinine ratio is a measure of kidney damage, and used to diagnose and stage chronic kidney disease. To extend the knowledge on regulatory mechanisms related to kidney function and disease, we conducted a blood-based epigenome-wide association study for estimated glomerular filtration rate (n = 33,605) and urinary albumin-to-creatinine ratio (n = 15,068) and detected 69 and seven CpG sites where DNA methylation was associated with the respective trait. The majority of these findings showed directionally consistent associations with the respective clinical outcomes chronic kidney disease and moderately increased albuminuria. Associations of DNA methylation with kidney function, such as CpGs at JAZF1, PELI1 and CHD2 were validated in kidney tissue. Methylation at PHRF1, LDB2, CSRNP1 and IRF5 indicated causal effects on kidney function. Enrichment analyses revealed pathways related to hemostasis and blood cell migration for estimated glomerular filtration rate, and immune cell activation and response for urinary albumin-to-creatinineratio-associated CpGs.", "doi": "10.1038/s41467-021-27234-3", "pmid": "34887417", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-021-27234-3"}], "notes": [], "created": "2021-12-22T19:39:46.207Z", "modified": "2021-12-22T19:39:47.563Z"}, {"entity": "publication", "iuid": "6cab2cbebcc34f5e8cc965eb5955fdca", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6cab2cbebcc34f5e8cc965eb5955fdca.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6cab2cbebcc34f5e8cc965eb5955fdca"}}, "title": "Genetically determined NLRP3 inflammasome activation associates with systemic inflammation and cardiovascular mortality.", "authors": [{"family": "Schunk", "given": "Stefan J", "initials": "SJ"}, {"family": "Kleber", "given": "Marcus E", "initials": "ME", "orcid": "0000-0003-0663-7275", "researcher": {"href": "https://publications.scilifelab.se/researcher/a51175112cfb4721b8c9fbfdc71c4307.json"}}, {"family": "M\u00e4rz", "given": "Winfried", "initials": "W"}, {"family": "Pang", "given": "Shichao", "initials": "S", "orcid": "0000-0002-4111-2864", "researcher": {"href": "https://publications.scilifelab.se/researcher/9839ca383ecb432dafae190a3a5b583a.json"}}, {"family": "Zewinger", "given": "Stephen", "initials": "S"}, {"family": "Triem", "given": "Sarah", "initials": "S"}, {"family": "Ege", "given": "Philipp", "initials": "P"}, {"family": "Reichert", "given": "Matthias C", "initials": "MC", "orcid": "0000-0002-8192-0575", "researcher": {"href": "https://publications.scilifelab.se/researcher/a12ee4f4194f4f9c8cfecd585aa92fe9.json"}}, {"family": "Krawczyk", "given": "Marcin", "initials": "M"}, {"family": "Weber", "given": "Susanne N", "initials": "SN"}, {"family": "Jaumann", "given": "Isabella", "initials": "I"}, {"family": "Schmit", "given": "David", "initials": "D"}, {"family": "Sarakpi", "given": "Tamim", "initials": "T"}, {"family": "Wagenpfeil", "given": "Stefan", "initials": "S", "orcid": "0000-0002-4558-4041", "researcher": {"href": "https://publications.scilifelab.se/researcher/9587116dd42d44d9b5a1cc33af1d6623.json"}}, {"family": "Kramann", "given": "Rafael", "initials": "R", "orcid": "0000-0003-4048-6351", "researcher": {"href": "https://publications.scilifelab.se/researcher/d5994a0ef0594c55a01e0886f3288b3b.json"}}, {"family": "Boerwinkle", "given": "Eric", "initials": "E"}, {"family": "Ballantyne", "given": "Christie M", "initials": "CM"}, {"family": "Grove", "given": "Megan L", "initials": "ML"}, {"family": "Tragante", "given": "Vinicius", "initials": "V", "orcid": "0000-0002-8223-8957", "researcher": {"href": "https://publications.scilifelab.se/researcher/eb83d260bc8546edba9e3e2ed2d2c752.json"}}, {"family": "Pilbrow", "given": "Anna P", "initials": "AP", "orcid": "0000-0003-1949-9449", "researcher": {"href": "https://publications.scilifelab.se/researcher/b86a1225a68e403e806a07b42e96c991.json"}}, {"family": "Richards", "given": "A Mark", "initials": "AM", "orcid": "0000-0002-2023-8177", "researcher": {"href": "https://publications.scilifelab.se/researcher/305e1cdb095145fab591d41542b578dd.json"}}, {"family": "Cameron", "given": "Vicky A", "initials": "VA", "orcid": "0000-0003-3147-683X", "researcher": {"href": "https://publications.scilifelab.se/researcher/72d115e749a34e239c336c16e35fdd64.json"}}, {"family": "Doughty", "given": "Robert N", "initials": "RN"}, {"family": "Dub\u00e9", "given": "Marie-Pierre", "initials": "M"}, {"family": "Tardif", "given": "Jean-Claude", "initials": "J"}, {"family": "Feroz-Zada", "given": "Yassamin", "initials": "Y"}, {"family": "Sun", "given": "Maxine", "initials": "M"}, {"family": "Liu", "given": "Chang", "initials": "C", "orcid": "0000-0002-8918-7224", "researcher": {"href": "https://publications.scilifelab.se/researcher/994fa918eb6142fca1897858b7b56a06.json"}}, {"family": "Ko", "given": "Yi-An", "initials": "Y"}, {"family": "Quyyumi", "given": "Arshed A", "initials": "AA"}, {"family": "Hartiala", "given": "Jaana A", "initials": "JA", "orcid": "0000-0003-4883-9318", "researcher": {"href": "https://publications.scilifelab.se/researcher/f39400df71774cf8ae408eccbe34d981.json"}}, {"family": "Tang", "given": "W H Wilson", "initials": "WHW", "orcid": "0000-0002-8335-735X", "researcher": {"href": "https://publications.scilifelab.se/researcher/5aab6a5657004a79aeda81c22a077268.json"}}, {"family": "Hazen", "given": "Stanley L", "initials": "SL", "orcid": "0000-0001-7124-6639", "researcher": {"href": "https://publications.scilifelab.se/researcher/abce9cd916c94667a73bc348ede57a01.json"}}, {"family": "Allayee", "given": "Hooman", "initials": "H", "orcid": "0000-0002-2384-5239", "researcher": {"href": "https://publications.scilifelab.se/researcher/4f1c610874a248c8beaa2254d319c586.json"}}, {"family": "McDonough", "given": "Caitrin W", "initials": "CW", "orcid": "0000-0001-6393-7288", "researcher": {"href": "https://publications.scilifelab.se/researcher/61630ed695424fe9a15afa6b8d7d7362.json"}}, {"family": "Gong", "given": "Yan", "initials": "Y", "orcid": "0000-0002-8218-1620", "researcher": {"href": "https://publications.scilifelab.se/researcher/a2daf12201f64608b70dac45339da354.json"}}, {"family": "Cooper-DeHoff", "given": "Rhonda M", "initials": "RM"}, {"family": "Johnson", "given": "Julie A", "initials": "JA"}, {"family": "Scholz", "given": "Markus", "initials": "M", "orcid": "0000-0002-4059-1779", "researcher": {"href": "https://publications.scilifelab.se/researcher/53d7b0e2dcdb4361b54016cb1550c5fe.json"}}, {"family": "Teren", "given": "Andrej", "initials": "A"}, {"family": "Burkhardt", "given": "Ralph", "initials": "R", "orcid": "0000-0003-1924-1202", "researcher": {"href": "https://publications.scilifelab.se/researcher/abe3ddd140b3478485f44119d18926b7.json"}}, {"family": "Martinsson", "given": "Andreas", "initials": "A"}, {"family": "Smith", "given": "J Gustav", "initials": "JG"}, {"family": "Wallentin", "given": "Lars", "initials": "L", "orcid": "0000-0003-0378-6531", "researcher": {"href": "https://publications.scilifelab.se/researcher/388a76db2e4d423882d1cf2bf6b7d985.json"}}, {"family": "James", "given": "Stefan K", "initials": "SK"}, {"family": "Eriksson", "given": "Niclas", "initials": "N", "orcid": "0000-0002-2152-4343", "researcher": {"href": "https://publications.scilifelab.se/researcher/64611a83caba46d597f45371b77de26b.json"}}, {"family": "White", "given": "Harvey", "initials": "H", "orcid": "0000-0001-7712-6750", "researcher": {"href": "https://publications.scilifelab.se/researcher/3fe685eeba0d411f8d275e3ecbf4bb3c.json"}}, {"family": "Held", "given": "Claes", "initials": "C", "orcid": "0000-0001-9402-7404", "researcher": {"href": "https://publications.scilifelab.se/researcher/88c69f319fce4852aab37e02a75ed525.json"}}, {"family": "Waterworth", "given": "Dawn", "initials": "D", "orcid": "0000-0002-9226-1317", "researcher": {"href": "https://publications.scilifelab.se/researcher/9e78b8890897424abea48058cd4c77d2.json"}}, {"family": "Trompet", "given": "Stella", "initials": "S"}, {"family": "Jukema", "given": "J Wouter", "initials": "JW", "orcid": "0000-0002-3246-8359", "researcher": {"href": "https://publications.scilifelab.se/researcher/0479b794031d4df7bed96340b3470c19.json"}}, {"family": "Ford", "given": "Ian", "initials": "I", "orcid": "0000-0001-5927-1823", "researcher": {"href": "https://publications.scilifelab.se/researcher/317610dc46d14a2ebea4a1fc4e9cecc7.json"}}, {"family": "Stott", "given": "David J", "initials": "DJ", "orcid": "0000-0002-3110-7746", "researcher": {"href": "https://publications.scilifelab.se/researcher/c7e647358616409f9d8983f342485014.json"}}, {"family": "Sattar", "given": "Naveed", "initials": "N", "orcid": "0000-0002-1604-2593", "researcher": {"href": "https://publications.scilifelab.se/researcher/80fbc7cdcfc444acb066449f80f87181.json"}}, {"family": "Cresci", "given": "Sharon", "initials": "S", "orcid": "0000-0002-5417-1054", "researcher": {"href": "https://publications.scilifelab.se/researcher/e134fd37d561443eb2bd8c23c3aa6df9.json"}}, {"family": "Spertus", "given": "John A", "initials": "JA", "orcid": "0000-0002-2839-2611", "researcher": {"href": "https://publications.scilifelab.se/researcher/58934381001f467fa9c8ed53787956bb.json"}}, {"family": "Campbell", "given": "Hannah", "initials": "H"}, {"family": "Tierling", "given": "Sascha", "initials": "S"}, {"family": "Walter", "given": "J\u00f6rn", "initials": "J", "orcid": "0000-0003-0563-7417", "researcher": {"href": "https://publications.scilifelab.se/researcher/3ea3e512691b4aa39c5b7c7fdcdb585d.json"}}, {"family": "Ampofo", "given": "Emmanuel", "initials": "E"}, {"family": "Niemeyer", "given": "Barbara A", "initials": "BA", "orcid": "0000-0002-6963-0575", "researcher": {"href": "https://publications.scilifelab.se/researcher/f5261a56f977404b894cd4a5bad1bbc3.json"}}, {"family": "Lipp", "given": "Peter", "initials": "P", "orcid": "0000-0003-4728-9174", "researcher": {"href": "https://publications.scilifelab.se/researcher/b96abc30cbf54fc1917b2976308c12b3.json"}}, {"family": "Schunkert", "given": "Heribert", "initials": "H"}, {"family": "B\u00f6hm", "given": "Michael", "initials": "M"}, {"family": "Koenig", "given": "Wolfgang", "initials": "W", "orcid": "0000-0002-2064-9603", "researcher": {"href": "https://publications.scilifelab.se/researcher/b358f3d797814a07a05a63364ae37d27.json"}}, {"family": "Fliser", "given": "Danilo", "initials": "D"}, {"family": "Laufs", "given": "Ulrich", "initials": "U", "orcid": "0000-0003-2620-9323", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7b26e6a8964ce2b76be17eddf2c7ac.json"}}, {"family": "Speer", "given": "Thimoteus", "initials": "T", "orcid": "0000-0002-2491-6393", "researcher": {"href": "https://publications.scilifelab.se/researcher/4c3bc32b3f144c6080853bae7094d681.json"}}, {"family": "eQTLGen consortium", "given": "", "initials": ""}, {"family": "BIOS consortium", "given": "", "initials": ""}], "type": "journal article", "published": "2021-05-07", "journal": {"title": "Eur. Heart J.", "issn": "1522-9645", "issn-l": "0195-668X", "volume": "42", "issue": "18", "pages": "1742-1756"}, "abstract": "Inflammation plays an important role in cardiovascular disease (CVD) development. The NOD-like receptor protein-3 (NLRP3) inflammasome contributes to the development of atherosclerosis in animal models. Components of the NLRP3 inflammasome pathway such as interleukin-1\u03b2 can therapeutically be targeted. Associations of genetically determined inflammasome-mediated systemic inflammation with CVD and mortality in humans are unknown.\r\n\r\nWe explored the association of genetic NLRP3 variants with prevalent CVD and cardiovascular mortality in 538 167 subjects on the individual participant level in an explorative gene-centric approach without performing multiple testing. Functional relevance of single-nucleotide polymorphisms on NLRP3 inflammasome activation has been evaluated in monocyte-enriched peripheral blood mononuclear cells (PBMCs). Genetic analyses identified the highly prevalent (minor allele frequency 39.9%) intronic NLRP3 variant rs10754555 to affect NLRP3 gene expression. rs10754555 carriers showed significantly higher C-reactive protein and serum amyloid A plasma levels. Carriers of the G allele showed higher NLRP3 inflammasome activation in isolated human PBMCs. In carriers of the rs10754555 variant, the prevalence of coronary artery disease was significantly higher as compared to non-carriers with a significant interaction between rs10754555 and age. Importantly, rs10754555 carriers had significantly higher risk for cardiovascular mortality during follow-up. Inflammasome inducers (e.g. urate, triglycerides, apolipoprotein C3) modulated the association between rs10754555 and mortality.\r\n\r\nThe NLRP3 intronic variant rs10754555 is associated with increased systemic inflammation, inflammasome activation, prevalent coronary artery disease, and mortality. This study provides evidence for a substantial role of genetically driven systemic inflammation in CVD and highlights the NLRP3 inflammasome as a therapeutic target.", "doi": "10.1093/eurheartj/ehab107", "pmid": "33748830", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pii", "key": "6179517"}, {"db": "pmc", "key": "PMC8244638"}], "notes": [], "created": "2021-08-19T13:42:03.904Z", "modified": "2021-12-07T13:39:27.736Z"}, {"entity": "publication", "iuid": "c1a6d2301da54435a1c59494b1d09e4e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c1a6d2301da54435a1c59494b1d09e4e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c1a6d2301da54435a1c59494b1d09e4e"}}, "title": "Plasma proteins associated with cardiovascular death in patients with chronic coronary heart disease: A retrospective study.", "authors": [{"family": "Wallentin", "given": "Lars", "initials": "L", "orcid": "0000-0003-0378-6531", "researcher": {"href": "https://publications.scilifelab.se/researcher/388a76db2e4d423882d1cf2bf6b7d985.json"}}, {"family": "Eriksson", "given": "Niclas", "initials": "N", "orcid": "0000-0002-2152-4343", "researcher": {"href": "https://publications.scilifelab.se/researcher/64611a83caba46d597f45371b77de26b.json"}}, {"family": "Olszowka", "given": "Maciej", "initials": "M", "orcid": "0000-0001-6013-4519", "researcher": {"href": "https://publications.scilifelab.se/researcher/912f23a5cb3d458c84aaaaad4a2b45fd.json"}}, {"family": "Grammer", "given": "Tanja B", "initials": "TB"}, {"family": "Hagstr\u00f6m", "given": "Emil", "initials": "E", "orcid": "0000-0003-3221-0144", "researcher": {"href": "https://publications.scilifelab.se/researcher/9446657edc224584a7bdfd76c8d991cf.json"}}, {"family": "Held", "given": "Claes", "initials": "C", "orcid": "0000-0001-9402-7404", "researcher": {"href": "https://publications.scilifelab.se/researcher/88c69f319fce4852aab37e02a75ed525.json"}}, {"family": "Kleber", "given": "Marcus E", "initials": "ME", "orcid": "0000-0003-0663-7275", "researcher": {"href": "https://publications.scilifelab.se/researcher/a51175112cfb4721b8c9fbfdc71c4307.json"}}, {"family": "Koenig", "given": "Wolfgang", "initials": "W", "orcid": "0000-0002-2064-9603", "researcher": {"href": "https://publications.scilifelab.se/researcher/b358f3d797814a07a05a63364ae37d27.json"}}, {"family": "M\u00e4rz", "given": "Winfried", "initials": "W", "orcid": "0000-0001-6083-8946", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae0d0dd988e846c4b8c5869b9d1f2905.json"}}, {"family": "Stewart", "given": "Ralph A H", "initials": "RAH", "orcid": "0000-0002-6167-1225", "researcher": {"href": "https://publications.scilifelab.se/researcher/493d2ac878264e0d98736945d8fdbb4d.json"}}, {"family": "White", "given": "Harvey D", "initials": "HD"}, {"family": "\u00c5berg", "given": "Mikael", "initials": "M", "orcid": "0000-0002-7858-8233", "researcher": {"href": "https://publications.scilifelab.se/researcher/90fa86e9aeaa43ea9547e48b4f3f24e3.json"}}, {"family": "Siegbahn", "given": "Agneta", "initials": "A", "orcid": "0000-0003-3955-5671", "researcher": {"href": "https://publications.scilifelab.se/researcher/b04f7f66e31e4c369c078c4d5d0f2a89.json"}}], "type": "journal article", "published": "2021-01-00", "journal": {"title": "PLoS Med.", "issn": "1549-1676", "issn-l": "1549-1277", "volume": "18", "issue": "1", "pages": "e1003513"}, "abstract": "Circulating biomarkers are associated with the development of coronary heart disease (CHD) and its complications by reflecting pathophysiological pathways and/or organ dysfunction. We explored the associations between 157 cardiovascular (CV) and inflammatory biomarkers and CV death using proximity extension assays (PEA) in patients with chronic CHD.\n\nThe derivation cohort consisted of 605 cases with CV death and 2,788 randomly selected non-cases during 3-5 years follow-up included in the STabilization of Atherosclerotic plaque By Initiation of darapLadIb TherapY (STABILITY) trial between 2008 and 2010. The replication cohort consisted of 245 cases and 1,042 non-cases during 12 years follow-up included in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study between 1997 and 2000. Biomarker levels were measured with conventional immunoassays and/or with the OLINK PEA panels CVD I and Inflammation. Associations with CV death were evaluated by Random Survival Forest (RF) and Cox regression analyses. Both cohorts had the same median age (65 years) and 20% smokers, while there were slight differences in male sex (82% and 76%), hypertension (70% and 78%), and diabetes (39% and 30%) in the respective STABILITY and LURIC cohorts. The analyses identified 18 biomarkers with confirmed independent association with CV death by Boruta analyses and statistical significance (all p < 0.0001) by Cox regression when adjusted for clinical characteristics in both cohorts. Most prognostic information was carried by N-terminal prohormone of brain natriuretic peptide (NTproBNP), hazard ratio (HR for 1 standard deviation [SD] increase of the log scale of the distribution of the biomarker in the replication cohort) 2.079 (95% confidence interval [CI] 1.799-2.402), and high-sensitivity troponin T (cTnT-hs) HR 1.715 (95% CI 1.491-1.973). The other proteins with independent associations were growth differentiation factor 15 (GDF-15) HR 1.728 (95% CI 1.527-1.955), transmembrane immunoglobulin and mucin domain protein (TIM-1) HR 1.555 (95% CI 1.362-1.775), renin HR 1.501 (95% CI 1.305-1.727), osteoprotegerin (OPG) HR 1.488 (95% CI 1.297-1.708), soluble suppression of tumorigenesis 2 protein (sST2) HR 1.478 (95% CI 1.307-1.672), cystatin-C (Cys-C) HR 1.370 (95% CI 1.243-1.510), tumor necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAIL-R2) HR 1.205 (95% CI 1.131-1.285), carbohydrate antigen 125 (CA-125) HR 1.347 (95% CI 1.226-1.479), brain natriuretic peptide (BNP) HR 1.399 (95% CI 1.255-1.561), interleukin 6 (IL-6) HR 1.478 (95% CI 1.316-1.659), hepatocyte growth factor (HGF) HR 1.259 (95% CI 1.134-1.396), spondin-1 HR 1.295 (95% CI 1.156-1.450), fibroblast growth factor 23 (FGF-23) HR 1.349 (95% CI 1.237-1.472), chitinase-3 like protein 1 (CHI3L1) HR 1.284 (95% CI 1.129-1.461), tumor necrosis factor receptor 1 (TNF-R1) HR 1.486 (95% CI 1.307-1.689), and adrenomedullin (AM) HR 1.750 (95% CI 1.490-2.056). The study is limited by the differences in design, size, and length of follow-up of the 2 studies and the lack of results from coronary angiograms and follow-up of nonfatal events.\n\nProfiles of levels of multiple plasma proteins might be useful for the identification of different pathophysiological pathways associated with an increased risk of CV death in patients with chronic CHD.\n\nClinicalTrials.gov NCT00799903.", "doi": "10.1371/journal.pmed.1003513", "pmid": "33439866", "labels": {"Affinity Proteomics Uppsala": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7817029"}, {"db": "pii", "key": "PMEDICINE-D-20-04160"}, {"db": "ClinicalTrials.gov", "key": "NCT00799903"}], "notes": [], "created": "2021-12-10T09:23:14.354Z", "modified": "2022-12-02T09:03:46.477Z"}]}