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"Lakatta", "given": "Edward L M", "initials": "ELM", "orcid": "0000-0002-4772-0035", "researcher": {"href": "https://publications.scilifelab.se/researcher/bc797241e3fa45d7b9d8438568414f2a.json"}}, {"family": "Cheng", "given": "Ching-Yu", "initials": "C"}, {"family": "D\u00f6rr", "given": "Marcus", "initials": "M", "orcid": "0000-0001-7471-475X", "researcher": {"href": "https://publications.scilifelab.se/researcher/346fa1fbeb2e474b94f189d52d7cfb1c.json"}}, {"family": "Wong", "given": "Tien-Yin", "initials": "T"}, {"family": "Sabanayagam", "given": "Charumathi", "initials": "C", "orcid": "0000-0002-4042-4719", "researcher": {"href": "https://publications.scilifelab.se/researcher/a5ac2397f6b14194949f4dbb92a21eba.json"}}, {"family": "Oldehinkel", "given": "Albertine J", "initials": "AJ", "orcid": "0000-0003-3925-3913", "researcher": {"href": "https://publications.scilifelab.se/researcher/65ee5f9938f547bcbe51cbaf5fd7a9ba.json"}}, {"family": "Riese", "given": "Harriette", "initials": "H"}, {"family": "Lehtim\u00e4ki", "given": "Terho", "initials": "T", "orcid": "0000-0002-2555-4427", "researcher": {"href": "https://publications.scilifelab.se/researcher/03ed59707dae4c8fb9e63ac1f7c398e3.json"}}, {"family": "Verweij", "given": "Niek", "initials": "N"}, {"family": "van der Harst", "given": "Pim", "initials": "P"}], "type": "meta-analysis", "published": "2023-08-02", "journal": {"title": "Nat Commun", "issn": "2041-1723", "issn-l": "2041-1723", "volume": "14", "issue": "1", "pages": "4646"}, "abstract": "Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.", "doi": "10.1038/s41467-023-39521-2", "pmid": "37532724", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service", "NGI SNP genotyping": "Service", "Clinical Genomics Gothenburg": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC10397318"}, {"db": "pii", "key": "10.1038/s41467-023-39521-2"}], "notes": [], "created": "2023-08-14T06:18:27.304Z", "modified": "2023-11-30T22:39:21.180Z"}, {"entity": "publication", "iuid": "a85b4e387fa944659cfb0c8c1c5b47ad", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a85b4e387fa944659cfb0c8c1c5b47ad.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a85b4e387fa944659cfb0c8c1c5b47ad"}}, "title": "Stroke genetics informs drug discovery and risk prediction across ancestries.", "authors": [{"family": "Mishra", "given": "Aniket", "initials": "A", "orcid": "0000-0002-8141-1543", "researcher": {"href": "https://publications.scilifelab.se/researcher/5e95668f120440e5bb3ea9554377aa69.json"}}, {"family": "Malik", "given": "Rainer", "initials": "R"}, {"family": "Hachiya", "given": "Tsuyoshi", "initials": "T", "orcid": "0000-0002-5274-3266", "researcher": {"href": "https://publications.scilifelab.se/researcher/052c404d92294a5794513bbd8bf9ad44.json"}}, {"family": "J\u00fcrgenson", "given": "Tuuli", "initials": "T"}, {"family": "Namba", "given": "Shinichi", "initials": "S", "orcid": "0000-0002-7486-3146", "researcher": {"href": "https://publications.scilifelab.se/researcher/2e3a77716d0947eca303cb3a836e7606.json"}}, {"family": "Posner", "given": "Daniel C", "initials": "DC", "orcid": "0000-0002-3056-6924", "researcher": {"href": "https://publications.scilifelab.se/researcher/4b23b7f5718543519b63b5f5241270b1.json"}}, {"family": "Kamanu", "given": "Frederick 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"initials": "JE", "orcid": "0000-0002-9672-2491", "researcher": {"href": "https://publications.scilifelab.se/researcher/cfa4efb5afae47528265d8be0d5e67fd.json"}}, {"family": "Milani", "given": "Lili", "initials": "L", "orcid": "0000-0002-5323-3102", "researcher": {"href": "https://publications.scilifelab.se/researcher/dec8d00c4b9d43458c5c895b164695d5.json"}}, {"family": "Kamatani", "given": "Yoichiro", "initials": "Y"}, {"family": "Dichgans", "given": "Martin", "initials": "M", "orcid": "0000-0002-0654-387X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f41f224e973440f6a78a49b54ca35e3a.json"}}, {"family": "Debette", "given": "Stephanie", "initials": "S"}], "type": "journal article", "published": "2022-11-00", "journal": {"title": "Nature", "issn": "1476-4687", "volume": "611", "issue": "7934", "pages": "115-123", "issn-l": "0028-0836"}, "abstract": "Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.", "doi": "10.1038/s41586-022-05165-3", "pmid": "36180795", "labels": {"National Genomics Infrastructure": "Service", "NGI SNP genotyping": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41586-022-05165-3"}, {"db": "pmc", "key": "PMC9524349"}], "notes": [], "created": "2022-11-09T14:36:41.202Z", "modified": "2022-11-09T14:37:47.411Z"}, {"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": "https://publications.scilifelab.se/researcher/b9c33ed3b64348be904a14698402445e.json"}}, {"family": "Hoppmann", "given": "Anselm", "initials": "A"}, {"family": "Chu", "given": "Audrey Y", "initials": "AY"}, {"family": "Tayo", "given": "Bamidele", "initials": "B"}, {"family": "Thio", "given": "Chris H L", "initials": "CHL"}, {"family": "Cusi", "given": "Daniele", "initials": "D"}, {"family": "Chai", "given": "Jin-Fang", "initials": "JF"}, {"family": "Sieber", "given": "Karsten B", "initials": "KB"}, {"family": "Horn", "given": "Katrin", "initials": "K"}, {"family": "Li", "given": "Man", "initials": "M"}, {"family": "Scholz", "given": "Markus", "initials": "M"}, {"family": "Cocca", "given": "Massimiliano", "initials": "M", "orcid": "0000-0002-1127-7596", "researcher": {"href": "https://publications.scilifelab.se/researcher/86431d25a54645e3988674b5e0ef6a59.json"}}, {"family": "Wuttke", "given": "Matthias", "initials": "M"}, {"family": "van der Most", "given": "Peter J", "initials": "PJ", "orcid": "0000-0001-8450-3518", "researcher": {"href": "https://publications.scilifelab.se/researcher/17cd11842111490ba5460f3093a366f3.json"}}, {"family": "Yang", "given": "Qiong", "initials": "Q", "orcid": "0000-0002-3658-1375", "researcher": {"href": "https://publications.scilifelab.se/researcher/430f81a2a8334a0e887346376b2f530e.json"}}, {"family": "Ghasemi", "given": "Sahar", "initials": "S"}, {"family": "Nutile", "given": "Teresa", "initials": "T"}, {"family": "Li", "given": "Yong", "initials": "Y", "orcid": "0000-0003-2651-8791", "researcher": {"href": "https://publications.scilifelab.se/researcher/1c15132ea27d43a097e4f2672f5b00ce.json"}}, {"family": "Pontali", "given": "Giulia", "initials": "G", "orcid": "0000-0002-4521-8981", "researcher": {"href": "https://publications.scilifelab.se/researcher/e1522f9b9c404f7bb1313218a91c6779.json"}}, {"family": "G\u00fcnther", "given": "Felix", "initials": "F"}, {"family": "Dehghan", "given": "Abbas", "initials": "A", "orcid": "0000-0001-6403-016X", "researcher": {"href": "https://publications.scilifelab.se/researcher/a63be46a547c4b99a59d71bf59194790.json"}}, {"family": "Correa", "given": "Adolfo", "initials": "A"}, {"family": "Parsa", "given": "Afshin", "initials": "A"}, {"family": "Feresin", "given": "Agnese", "initials": "A"}, {"family": "de Vries", "given": "Aiko P J", "initials": "APJ"}, {"family": "Zonderman", "given": "Alan B", "initials": "AB"}, {"family": "Smith", "given": "Albert V", "initials": "AV", "orcid": "0000-0003-1942-5845", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b28739aa7d746718d670363d7c18a40.json"}}, {"family": "Oldehinkel", "given": "Albertine J", "initials": "AJ"}, {"family": "De Grandi", "given": "Alessandro", "initials": "A"}, {"family": "Rosenkranz", "given": "Alexander R", "initials": "AR"}, {"family": "Franke", "given": "Andre", "initials": "A", "orcid": "0000-0003-1530-5811", "researcher": {"href": "https://publications.scilifelab.se/researcher/8fffe3df068c4283a8b8b583717e6bb6.json"}}, {"family": "Teren", "given": "Andrej", "initials": "A"}, {"family": "Metspalu", "given": "Andres", "initials": "A", "orcid": "0000-0002-3718-796X", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd553a77a5a54258b4a4701f0e70a3f8.json"}}, {"family": "Hicks", "given": "Andrew A", "initials": "AA", "orcid": "0000-0001-6320-0411", "researcher": {"href": "https://publications.scilifelab.se/researcher/a679db3cfdb6408b8f1a009534d7b902.json"}}, {"family": "Morris", "given": "Andrew P", "initials": "AP"}, {"family": "T\u00f6njes", "given": "Anke", "initials": "A"}, {"family": "Morgan", "given": "Anna", "initials": "A"}, {"family": "Podgornaia", "given": "Anna I", "initials": "AI"}, {"family": "Peters", "given": "Annette", "initials": "A"}, {"family": "K\u00f6rner", "given": "Antje", "initials": "A"}, {"family": "Mahajan", "given": "Anubha", "initials": "A"}, {"family": "Campbell", "given": "Archie", "initials": "A"}, {"family": "Freedman", "given": "Barry I", "initials": "BI", "orcid": "0000-0003-0275-5530", "researcher": {"href": "https://publications.scilifelab.se/researcher/d30522bf1f794a9ab21b5bc757bc9fca.json"}}, {"family": "Spedicati", "given": "Beatrice", "initials": "B", "orcid": "0000-0002-7432-4708", "researcher": {"href": "https://publications.scilifelab.se/researcher/4b182b23b6be49deb7d46b4945474729.json"}}, {"family": "Ponte", "given": "Belen", "initials": "B"}, {"family": "Sch\u00f6ttker", "given": "Ben", "initials": "B"}, {"family": "Brumpton", "given": "Ben", "initials": "B", "orcid": "0000-0002-3058-1059", "researcher": {"href": "https://publications.scilifelab.se/researcher/da9d23aaf1dc4d18a0a13e4847ea9955.json"}}, {"family": "Banas", "given": "Bernhard", "initials": "B"}, {"family": "Kr\u00e4mer", "given": "Bernhard K", "initials": "BK"}, {"family": "Jung", "given": "Bettina", "initials": "B"}, {"family": "\u00c5svold", "given": "Bj\u00f8rn 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"https://publications.scilifelab.se/researcher/7b4ca0d34923489785f26c8071a7151d.json"}}, {"family": "Hayward", "given": "Caroline", "initials": "C", "orcid": "0000-0002-9405-9550", "researcher": {"href": "https://publications.scilifelab.se/researcher/cd49e9ad5a024c7ca2f1aa97d9e58eba.json"}}, {"family": "Spracklen", "given": "Cassandra N", "initials": "CN", "orcid": "0000-0003-3590-7182", "researcher": {"href": "https://publications.scilifelab.se/researcher/132c3af299ef430294d5d2091f135e90.json"}}, {"family": "Robinson-Cohen", "given": "Cassianne", "initials": "C"}, {"family": "Hartman", "given": "Catharina A", "initials": "CA"}, {"family": "Lindgren", "given": "Cecilia M", "initials": "CM"}, {"family": "Wang", "given": "Chaolong", "initials": "C", "orcid": "0000-0003-3945-1012", "researcher": {"href": "https://publications.scilifelab.se/researcher/ea6e6c8a06904e3dae39d08efa05234e.json"}}, {"family": "Sabanayagam", "given": "Charumathi", "initials": "C", "orcid": "0000-0002-4042-4719", "researcher": {"href": "https://publications.scilifelab.se/researcher/a5ac2397f6b14194949f4dbb92a21eba.json"}}, {"family": "Heng", "given": "Chew-Kiat", "initials": "CK", "orcid": "0000-0002-7309-9473", "researcher": {"href": "https://publications.scilifelab.se/researcher/a4e206bc73574cc1bcb4a9eb6c678d64.json"}}, {"family": "Lanzani", "given": "Chiara", "initials": "C"}, {"family": "Khor", "given": "Chiea-Chuen", "initials": "CC", "orcid": "0000-0002-1128-4729", "researcher": {"href": "https://publications.scilifelab.se/researcher/632dc088fb684153899441da97ec2ccd.json"}}, {"family": "Cheng", "given": "Ching-Yu", "initials": "CY", "orcid": "0000-0003-0655-885X", "researcher": {"href": "https://publications.scilifelab.se/researcher/cf94723ce7704692ac607327e86d4137.json"}}, {"family": "Fuchsberger", "given": "Christian", "initials": "C"}, {"family": "Gieger", "given": "Christian", "initials": "C", "orcid": "0000-0001-6986-9554", "researcher": {"href": "https://publications.scilifelab.se/researcher/86f44e76061c403fadd97b768e2a7e62.json"}}, {"family": "Shaffer", "given": "Christian M", "initials": "CM"}, {"family": "Schulz", "given": "Christina-Alexandra", "initials": "CA"}, {"family": "Willer", "given": "Cristen J", "initials": "CJ", "orcid": "0000-0001-5645-4966", "researcher": {"href": "https://publications.scilifelab.se/researcher/b3a8e1d33146452b87e7e21eb5339f80.json"}}, {"family": "Chasman", "given": "Daniel I", "initials": "DI"}, {"family": "Gudbjartsson", "given": "Daniel F", "initials": "DF"}, {"family": "Ruggiero", "given": "Daniela", "initials": "D"}, {"family": "Toniolo", "given": "Daniela", "initials": "D"}, {"family": "Czamara", "given": "Darina", "initials": "D", "orcid": "0000-0001-7381-904X", "researcher": {"href": "https://publications.scilifelab.se/researcher/0e9a8a7d605d4f63a311fc8a211422a6.json"}}, {"family": "Porteous", "given": "David J", "initials": "DJ", "orcid": "0000-0003-1249-6106", "researcher": {"href": "https://publications.scilifelab.se/researcher/b6e3ae11c02e4cb89e638e1e5ae0f50a.json"}}, {"family": "Waterworth", "given": "Dawn M", "initials": "DM"}, {"family": "Mascalzoni", "given": "Deborah", "initials": "D", "orcid": "0000-0003-4156-1464", "researcher": {"href": "https://publications.scilifelab.se/researcher/0301541bfe5844619d1d0486c58263f5.json"}}, {"family": "Mook-Kanamori", "given": "Dennis O", "initials": "DO"}, {"family": "Reilly", "given": "Dermot F", "initials": "DF"}, {"family": "Daw", "given": "E Warwick", "initials": "EW"}, {"family": "Hofer", "given": "Edith", "initials": "E"}, {"family": "Boerwinkle", "given": "Eric", "initials": "E"}, {"family": "Salvi", "given": "Erika", "initials": "E"}, {"family": "Bottinger", "given": "Erwin P", "initials": "EP"}, {"family": "Tai", "given": "E-Shyong", "initials": "ES", "orcid": "0000-0003-2929-8966", "researcher": {"href": "https://publications.scilifelab.se/researcher/6d2e26ed9b3848a386b1c6f0359d6917.json"}}, {"family": "Catamo", "given": "Eulalia", "initials": "E"}, {"family": "Rizzi", "given": "Federica", "initials": "F", "orcid": "0000-0002-4606-6553", "researcher": {"href": "https://publications.scilifelab.se/researcher/88dfc1951cef4148a64b4d5270bc97c5.json"}}, {"family": "Guo", "given": "Feng", "initials": "F"}, {"family": "Rivadeneira", "given": "Fernando", "initials": "F", "orcid": "0000-0001-9435-9441", "researcher": {"href": "https://publications.scilifelab.se/researcher/f8894904d3cf4671a2e563169829322a.json"}}, {"family": "Guilianini", "given": "Franco", "initials": "F"}, {"family": "Sveinbjornsson", "given": "Gardar", "initials": "G"}, {"family": "Ehret", "given": "Georg", "initials": "G"}, {"family": "Waeber", "given": "Gerard", "initials": "G"}, {"family": "Biino", "given": "Ginevra", "initials": "G"}, {"family": "Girotto", "given": "Giorgia", "initials": "G"}, {"family": "Pistis", "given": "Giorgio", "initials": "G"}, {"family": "Nadkarni", "given": "Girish N", "initials": "GN"}, {"family": "Delgado", "given": "Graciela E", "initials": "GE"}, {"family": "Montgomery", "given": "Grant W", "initials": "GW", "orcid": "0000-0002-4140-8139", "researcher": {"href": "https://publications.scilifelab.se/researcher/753ffaa3a5034b6a9f83d9b1c8c4729e.json"}}, {"family": "Snieder", "given": "Harold", "initials": "H", "orcid": "0000-0003-1949-2298", "researcher": {"href": "https://publications.scilifelab.se/researcher/e9276827839a4f3cb50dcaa2ad4708a5.json"}}, {"family": "Campbell", "given": "Harry", "initials": "H"}, {"family": "White", "given": "Harvey D", "initials": "HD"}, {"family": "Gao", "given": "He", "initials": "H"}, {"family": "Stringham", "given": "Heather M", "initials": "HM", "orcid": "0000-0002-2991-6392", "researcher": {"href": "https://publications.scilifelab.se/researcher/11c31e4ebda845a2834bac7c4916bca7.json"}}, {"family": "Schmidt", "given": "Helena", "initials": "H", "orcid": "0000-0001-9773-9992", "researcher": {"href": 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"initials": "JP"}, {"family": "Wilson", "given": "James F", "initials": "JF", "orcid": "0000-0001-5751-9178", "researcher": {"href": "https://publications.scilifelab.se/researcher/b39e6e0f7210494cb4f80be0f7413b6f.json"}}, {"family": "Halbritter", "given": "Jan", "initials": "J"}, {"family": "Felix", "given": "Janine F", "initials": "JF", "orcid": "0000-0002-9801-5774", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a4482378cb24a9f832729f7004a41bf.json"}}, {"family": "Divers", "given": "Jasmin", "initials": "J"}, {"family": "Kooner", "given": "Jaspal S", "initials": "JS", "orcid": "0000-0003-2086-4837", "researcher": {"href": "https://publications.scilifelab.se/researcher/73c5749dbce143f3aaf7e80b89ec9dd6.json"}}, {"family": "Lee", "given": "Jeannette Jen-Mai", "initials": "JJ"}, {"family": "O'Connell", "given": "Jeffrey", "initials": "J"}, {"family": "Rotter", "given": "Jerome I", "initials": "JI"}, {"family": "Liu", "given": "Jianjun", "initials": "J", "orcid": 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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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"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": "e389be71822d45d6ac04d848bfb48df6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e389be71822d45d6ac04d848bfb48df6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e389be71822d45d6ac04d848bfb48df6"}}, "title": "The power of genetic diversity in genome-wide association studies of lipids.", "authors": [{"family": "Graham", "given": "Sarah E", "initials": "SE", "orcid": "0000-0003-1271-2489", "researcher": {"href": "https://publications.scilifelab.se/researcher/9e302d0cabab449caf7efca024e6d627.json"}}, {"family": "Clarke", "given": "Shoa L", "initials": "SL", "orcid": "0000-0002-6592-1172", "researcher": {"href": "https://publications.scilifelab.se/researcher/91e526cf78cf4323b8625e5bfe7728e1.json"}}, {"family": "Wu", "given": "Kuan-Han H", "initials": "KH", "orcid": "0000-0003-4286-4299", "researcher": {"href": "https://publications.scilifelab.se/researcher/44072ea2199c47d9a24c368b90439a06.json"}}, {"family": "Kanoni", "given": "Stavroula", "initials": "S", "orcid": "0000-0002-1691-9615", "researcher": {"href": "https://publications.scilifelab.se/researcher/95f9c5fce1fe44719ef772eda9a4f5e4.json"}}, {"family": "Zajac", "given": "Greg J M", "initials": "GJM", "orcid": "0000-0001-6411-9666", "researcher": {"href": "https://publications.scilifelab.se/researcher/3a903723e08040f5b9eb0086fdcbdcd2.json"}}, {"family": "Ramdas", "given": 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"https://publications.scilifelab.se/researcher/b75640c684a2457c9e5ebcf472b01dea.json"}}, {"family": "Kubo", "given": "Michiaki", "initials": "M"}, {"family": "Kamatani", "given": "Yoichiro", "initials": "Y"}, {"family": "Okada", "given": "Yukinori", "initials": "Y", "orcid": "0000-0002-0311-8472", "researcher": {"href": "https://publications.scilifelab.se/researcher/40b13860bfef41959c29be2de853b456.json"}}, {"family": "Murakami", "given": "Yoshinori", "initials": "Y"}, {"family": "Thorsteinsdottir", "given": "Unnur", "initials": "U"}, {"family": "Stefansson", "given": "Kari", "initials": "K"}, {"family": "Ho", "given": "Yuk-Lam", "initials": "YL"}, {"family": "Lynch", "given": "Julie A", "initials": "JA"}, {"family": "Rader", "given": "Daniel J", "initials": "DJ"}, {"family": "Tsao", "given": "Philip S", "initials": "PS"}, {"family": "Chang", "given": "Kyong-Mi", "initials": "KM"}, {"family": "Cho", "given": "Kelly", "initials": "K"}, {"family": "O'Donnell", "given": "Christopher J", "initials": "CJ"}, {"family": "Gaziano", "given": "John M", "initials": "JM"}, {"family": "Wilson", "given": "Peter", "initials": "P"}, {"family": "Rotimi", "given": "Charles N", "initials": "CN", "orcid": "0000-0001-5759-053X", "researcher": {"href": "https://publications.scilifelab.se/researcher/7fa2951fdebf4fddaad296d49b8f3f2b.json"}}, {"family": "Hazelhurst", "given": "Scott", "initials": "S"}, {"family": "Ramsay", "given": "Mich\u00e8le", "initials": "M", "orcid": "0000-0002-4156-4801", "researcher": {"href": "https://publications.scilifelab.se/researcher/31f970ff8b574a2290447b9626411d63.json"}}, {"family": "Trembath", "given": "Richard C", "initials": "RC"}, {"family": "van Heel", "given": "David A", "initials": "DA", "orcid": "0000-0002-0637-2265", "researcher": {"href": "https://publications.scilifelab.se/researcher/487906b4266443eab6fbe65e942bb5fe.json"}}, {"family": "Tamiya", "given": "Gen", "initials": "G"}, {"family": "Yamamoto", "given": "Masayuki", "initials": "M", "orcid": "0000-0002-9073-9436", "researcher": {"href": "https://publications.scilifelab.se/researcher/c566d57cdf9b43498cd9583fbb6c4c73.json"}}, {"family": "Kim", "given": "Bong-Jo", "initials": "BJ"}, {"family": "Mohlke", "given": "Karen L", "initials": "KL", "orcid": "0000-0001-6721-153X", "researcher": {"href": "https://publications.scilifelab.se/researcher/7c11d7ab911243edb9e2696efd95ecd4.json"}}, {"family": "Frayling", "given": "Timothy M", "initials": "TM"}, {"family": "Hirschhorn", "given": "Joel N", "initials": "JN", "orcid": "0000-0002-1650-7901", "researcher": {"href": "https://publications.scilifelab.se/researcher/79e3bb42733c4904a4543cb3b6397c0f.json"}}, {"family": "Kathiresan", "given": "Sekar", "initials": "S"}, {"family": "VA Million Veteran Program", "given": "", "initials": ""}, {"family": "Global Lipids Genetics Consortium*", "given": "", "initials": ""}, {"family": "Boehnke", "given": "Michael", "initials": "M", "orcid": "0000-0002-6442-7754", "researcher": {"href": "https://publications.scilifelab.se/researcher/b8cb72bdcea4492199a1b9d8ac406ac7.json"}}, {"family": "Natarajan", "given": "Pradeep", "initials": "P"}, {"family": "Peloso", "given": "Gina M", "initials": "GM", "orcid": "0000-0002-5355-8636", "researcher": {"href": "https://publications.scilifelab.se/researcher/3a0c07ebec3741efa6ef71d416e7c66a.json"}}, {"family": "Brown", "given": "Christopher D", "initials": "CD"}, {"family": "Morris", "given": "Andrew P", "initials": "AP", "orcid": "0000-0002-6805-6014", "researcher": {"href": "https://publications.scilifelab.se/researcher/991fd686a4a040a1a197c1f32d5b731b.json"}}, {"family": "Assimes", "given": "Themistocles L", "initials": "TL", "orcid": "0000-0003-2349-0009", "researcher": {"href": "https://publications.scilifelab.se/researcher/9e155ca3dd01486580be888d1ded405c.json"}}, {"family": "Deloukas", "given": "Panos", "initials": "P", "orcid": "0000-0001-9251-070X", "researcher": {"href": "https://publications.scilifelab.se/researcher/eb59dbd2f2204d41b801c41188611a9e.json"}}, {"family": "Sun", "given": "Yan V", "initials": "YV", "orcid": "0000-0002-2838-1824", "researcher": {"href": "https://publications.scilifelab.se/researcher/c6299caf6b6342fdbfab4c0d9738b28f.json"}}, {"family": "Willer", "given": "Cristen J", "initials": "CJ", "orcid": "0000-0001-5645-4966", "researcher": {"href": "https://publications.scilifelab.se/researcher/b3a8e1d33146452b87e7e21eb5339f80.json"}}], "type": "journal article", "published": "2021-12-00", "journal": {"title": "Nature", "issn": "1476-4687", "volume": "600", "issue": "7890", "pages": "675-679", "issn-l": "0028-0836"}, "abstract": "Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use1. Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels2, heart disease remains the leading cause of death worldwide3. Genome-wideassociation studies (GWAS) of blood lipid levels have led to important biological and clinical insights, as well as new drug targets, for cardiovascular disease. However, most previous GWAS4-23 have been conducted in European ancestry populations and may have missed genetic variants that contribute to lipid-level variation in other ancestry groups. These include differences in allele frequencies, effect sizes and linkage-disequilibrium patterns24. Here we conduct a multi-ancestry, genome-wide genetic discovery meta-analysis of lipid levels in approximately 1.65 million individuals, including 350,000 of non-European ancestries. We quantify the gain in studying non-European ancestries and provide evidence to support the expansion of recruitment of additional ancestries, even with relatively small sample sizes. We find that increasing diversity rather than studying additional individuals of European ancestry results in substantial improvements in fine-mapping functional variants and portability of polygenic prediction (evaluated in approximately 295,000 individuals from 7 ancestry groupings). Modest gains in the number of discovered loci and ancestry-specific variants were also achieved. As GWAS expand emphasis beyond the identification of genes and fundamental biology towards the use of genetic variants for preventive and precision medicine25, we anticipate that increased diversity of participants will lead to more accurate and equitable26 application of polygenic scores in clinical practice.", "doi": "10.1038/s41586-021-04064-3", "pmid": "34887591", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "mid", "key": "NIHMS1758809"}, {"db": "pmc", "key": "PMC8730582"}, {"db": "pii", "key": "10.1038/s41586-021-04064-3"}], "notes": [], "created": "2021-12-22T19:39:50.082Z", "modified": "2023-06-19T12:31:07.699Z"}]}