{"entity": "journal", "iuid": "a5d27283b4c14d27a6dddc1d6be70a5c", "timestamp": "2026-08-13T18:08:07.028Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/Circulation.json"}, "display": {"href": "https://publications.scilifelab.se/journal/Circulation"}}, "title": "Circulation", "issn": "1524-4539", "issn-l": "0009-7322", "publications_count": 8, "publications": [{"entity": "publication", "iuid": "0f40db40a4a744a193d075e875abdbf1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0f40db40a4a744a193d075e875abdbf1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0f40db40a4a744a193d075e875abdbf1"}}, "title": "Genetic Landscape of the ACE2 Coronavirus Receptor.", "authors": [{"family": "Yang", "given": "Zhijian", "initials": "Z", "orcid": "0000-0003-4803-8633", "researcher": {"href": "https://publications.scilifelab.se/researcher/104e44a8c1e949d18d371fad8b2c9fa9.json"}}, {"family": "Macdonald-Dunlop", "given": 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"initials": "JM", "orcid": "0000-0001-8141-8449", "researcher": {"href": "https://publications.scilifelab.se/researcher/aba5822711b246b397fffacb7ae403b3.json"}}, {"family": "Butterworth", "given": "Adam S", "initials": "AS", "orcid": "0000-0002-6915-9015", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b8c140c80d942c4b1b684876e4d6180.json"}}, {"family": "Micha\u00eblsson", "given": "Karl", "initials": "K", "orcid": "0000-0003-2815-1217", "researcher": {"href": "https://publications.scilifelab.se/researcher/eff63868e95240f695d47e871e31947f.json"}}, {"family": "Pawitan", "given": "Yudi", "initials": "Y"}, {"family": "Joshi", "given": "Peter K", "initials": "PK", "orcid": "0000-0002-6361-5059", "researcher": {"href": "https://publications.scilifelab.se/researcher/46050ddec8f64054b3bab46c5016aebf.json"}}, {"family": "Baillie", "given": "J Kenneth", "initials": "JK"}, {"family": "M\u00e4larstig", "given": "Anders", "initials": "A"}, {"family": "Reiner", "given": "Alexander P", "initials": "AP", "orcid": "0000-0002-1427-4470", "researcher": {"href": "https://publications.scilifelab.se/researcher/931fcf4444904ec398a450a9ec4f4389.json"}}, {"family": "Wilson", "given": "James F", "initials": "JF"}, {"family": "Shen", "given": "Xia", "initials": "X", "orcid": "0000-0003-4390-1979", "researcher": {"href": "https://publications.scilifelab.se/researcher/b40d1f7f07ed482b9c95f56c61f0a836.json"}}], "type": "journal article", "published": "2022-05-03", "journal": {"title": "Circulation", "issn": "1524-4539", "volume": "145", "issue": "18", "pages": "1398-1411", "issn-l": "0009-7322"}, "abstract": "SARS-CoV-2, the causal agent of COVID-19, enters human cells using the ACE2 (angiotensin-converting enzyme 2) protein as a receptor. ACE2 is thus key to the infection and treatment of the coronavirus. ACE2 is highly expressed in the heart and respiratory and gastrointestinal tracts, playing important regulatory roles in the cardiovascular and other biological systems. However, the genetic basis of the ACE2 protein levels is not well understood.\n\nWe have conducted the largest genome-wide association meta-analysis of plasma ACE2 levels in >28 000 individuals of the SCALLOP Consortium (Systematic and Combined Analysis of Olink Proteins). We summarize the cross-sectional epidemiological correlates of circulating ACE2. Using the summary statistics-based high-definition likelihood method, we estimate relevant genetic correlations with cardiometabolic phenotypes, COVID-19, and other human complex traits and diseases. We perform causal inference of soluble ACE2 on vascular disease outcomes and COVID-19 severity using mendelian randomization. We also perform in silico functional analysis by integrating with other types of omics data.\n\nWe identified 10 loci, including 8 novel, capturing 30% of the heritability of the protein. We detected that plasma ACE2 was genetically correlated with vascular diseases, severe COVID-19, and a wide range of human complex diseases and medications. An X-chromosome cis-protein quantitative trait loci-based mendelian randomization analysis suggested a causal effect of elevated ACE2 levels on COVID-19 severity (odds ratio, 1.63 [95% CI, 1.10-2.42]; P=0.01), hospitalization (odds ratio, 1.52 [95% CI, 1.05-2.21]; P=0.03), and infection (odds ratio, 1.60 [95% CI, 1.08-2.37]; P=0.02). Tissue- and cell type-specific transcriptomic and epigenomic analysis revealed that the ACE2 regulatory variants were enriched for DNA methylation sites in blood immune cells.\n\nHuman plasma ACE2 shares a genetic basis with cardiovascular disease, COVID-19, and other related diseases. The genetic architecture of the ACE2 protein is mapped, providing a useful resource for further biological and clinical studies on this coronavirus receptor.", "doi": "10.1161/CIRCULATIONAHA.121.057888", "pmid": "35387486", "labels": {"National Genomics Infrastructure": "Service", "NGI SNP genotyping": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Affinity Proteomics Stockholm": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9047645"}], "notes": [], "created": "2022-05-06T10:18:12.729Z", "modified": "2022-12-05T01:33:32.862Z"}, {"entity": "publication", "iuid": "0b34b7db41124b8eb5f36bf6e8077154", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0b34b7db41124b8eb5f36bf6e8077154.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0b34b7db41124b8eb5f36bf6e8077154"}}, "title": "Palmdelphin Regulates Nuclear Resilience to Mechanical Stress in the Endothelium.", "authors": [{"family": "S\u00e1inz-Jaspeado", "given": "Miguel", "initials": "M"}, {"family": "Smith", "given": "Ross O", "initials": "RO", "orcid": "0000-0003-4239-3204", "researcher": {"href": "https://publications.scilifelab.se/researcher/a464f28ad47c4706a08645b9616198b7.json"}}, {"family": "Plunde", "given": "Oscar", "initials": "O"}, {"family": "Pawelzik", "given": "Sven-Christian", "initials": "SC"}, {"family": "Jin", "given": "Yi", "initials": "Y", "orcid": "0000-0001-9704-973X", "researcher": {"href": "https://publications.scilifelab.se/researcher/deff30d686dd469f907bc80b8f628390.json"}}, {"family": "Nordling", "given": "Sofia", "initials": "S"}, {"family": "Ding", "given": "Yindi", "initials": "Y", "orcid": "0000-0003-4672-7611", "researcher": {"href": "https://publications.scilifelab.se/researcher/cda52c187d0e49f4b1f09b76bbfa0202.json"}}, {"family": "Aspenstr\u00f6m", "given": "Pontus", "initials": "P"}, {"family": "Hedlund", "given": "Marie", "initials": "M"}, {"family": "Bastianello", "given": "Giulia", "initials": "G"}, {"family": "Ascione", "given": "Flora", "initials": "F"}, {"family": "Li", "given": "Qingsen", "initials": "Q"}, {"family": "Demir", "given": "Cansaran Saygili", "initials": "CS"}, {"family": "Fernando", "given": "Dinesh", "initials": "D", "orcid": "0000-0003-2487-0599", "researcher": {"href": "https://publications.scilifelab.se/researcher/85093375f68a4e70912f07bb5c05ad48.json"}}, {"family": "Daniel", "given": "Geoffrey", "initials": "G", "orcid": "0000-0002-8886-1942", "researcher": {"href": "https://publications.scilifelab.se/researcher/628aeb01d86b47c1b09e2d070356dde8.json"}}, {"family": "Franco-Cereceda", "given": "Anders", "initials": "A"}, {"family": "Kroon", "given": "Jeffrey", "initials": "J", "orcid": "0000-0001-9983-6614", "researcher": {"href": "https://publications.scilifelab.se/researcher/df348c68131743d1a78d5058aacd20b4.json"}}, {"family": "Foiani", "given": "Marco", "initials": "M"}, {"family": "Petrova", "given": "Tatiana V", "initials": "TV"}, {"family": "Kilimann", "given": "Manfred W", "initials": "MW"}, {"family": "B\u00e4ck", "given": "Magnus", "initials": "M", "orcid": "0000-0003-0853-5141", "researcher": {"href": "https://publications.scilifelab.se/researcher/2208efeca524405f8162841b2d2e5910.json"}}, {"family": "Claesson-Welsh", "given": "Lena", "initials": "L", "orcid": "0000-0003-4275-2000", "researcher": {"href": "https://publications.scilifelab.se/researcher/647e2a349efd4e11827209883e86079b.json"}}], "type": "journal article", "published": "2021-11-16", "journal": {"title": "Circulation", "issn": "1524-4539", "issn-l": "0009-7322", "volume": "144", "issue": "20", "pages": "1629-1645"}, "abstract": "PALMD (palmdelphin) belongs to the family of paralemmin proteins implicated in cytoskeletal regulation. Single nucleotide polymorphisms in the PALMD locus that result in reduced expression are strong risk factors for development of calcific aortic valve stenosis and predict severity of the disease.\n\nImmunodetection and public database screening showed dominant expression of PALMD in endothelial cells (ECs) in brain and cardiovascular tissues including aortic valves. Mass spectrometry, coimmunoprecipitation, and immunofluorescent staining allowed identification of PALMD partners. The consequence of loss of PALMD expression was assessed in small interferring RNA-treated EC cultures, knockout mice, and human valve samples. RNA sequencing of ECs and transcript arrays on valve samples from an aortic valve study cohort including patients with the single nucleotide polymorphism rs7543130 informed about gene regulatory changes.\n\nECs express the cytosolic PALMD-KKVI splice variant, which associated with RANGAP1 (RAN GTP hydrolyase activating protein 1). RANGAP1 regulates the activity of the GTPase RAN and thereby nucleocytoplasmic shuttling via XPO1 (Exportin1). Reduced PALMD expression resulted in subcellular relocalization of RANGAP1 and XPO1, and nuclear arrest of the XPO1 cargoes p53 and p21. This indicates an important role for PALMD in nucleocytoplasmic transport and consequently in gene regulation because of the effect on localization of transcriptional regulators. Changes in EC responsiveness on loss of PALMD expression included failure to form a perinuclear actin cap when exposed to flow, indicating lack of protection against mechanical stress. Loss of the actin cap correlated with misalignment of the nuclear long axis relative to the cell body, observed in PALMD-deficient ECs, Palmd mouse aorta, and human aortic valve samples derived from patients with calcific aortic valve stenosis. In agreement with these changes in EC behavior, gene ontology analysis showed enrichment of nuclear- and cytoskeleton-related terms in -/-PALMD-silenced ECs.\n\nWe identify RANGAP1 as a PALMD partner in ECs. Disrupting the PALMD/RANGAP1 complex alters the subcellular localization of RANGAP1 and XPO1, and leads to nuclear arrest of the XPO1 cargoes p53 and p21, accompanied by gene regulatory changes and loss of actin-dependent nuclear resilience. Combined, these consequences of reduced PALMD expression provide a mechanistic underpinning for PALMD's contribution to calcific aortic valve stenosis pathology.", "doi": "10.1161/CIRCULATIONAHA.121.054182", "pmid": "34636652", "labels": {"Global Proteomics and Proteogenomics": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service", "Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC8589083"}], "notes": [], "created": "2022-03-29T10:27:37.036Z", "modified": "2023-11-16T12:06:34.222Z"}, {"entity": "publication", "iuid": "d04f44cd62564eadad0ce47ce505ff71", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d04f44cd62564eadad0ce47ce505ff71.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d04f44cd62564eadad0ce47ce505ff71"}}, "title": "Association of Factor V Leiden With Subsequent Atherothrombotic Events: A GENIUS-CHD Study of Individual Participant Data.", "authors": [{"family": "Mahmoodi", "given": "Bakhtawar K", "initials": "BK"}, {"family": "Tragante", "given": "Vinicius", "initials": "V"}, {"family": "Kleber", "given": "Marcus E", "initials": "ME"}, {"family": "Holmes", "given": "Michael V", "initials": "MV"}, {"family": "Schmidt", "given": "Amand F", "initials": "AF"}, {"family": "McCubrey", "given": "Raymond O", "initials": "RO"}, {"family": "Howe", "given": "Laurence J", "initials": "LJ"}, {"family": "Direk", "given": "Kenan", "initials": "K"}, {"family": "Allayee", "given": "Hooman", "initials": "H"}, {"family": "Baranova", "given": "Ekaterina V", "initials": "EV"}, {"family": "Braund", "given": "Peter S", "initials": "PS"}, {"family": "Delgado", "given": "Graciela E", "initials": "GE"}, {"family": "Eriksson", "given": "Niclas", "initials": "N"}, {"family": "Gijsberts", "given": "Crystel M", "initials": "CM"}, {"family": "Gong", "given": "Yan", "initials": "Y"}, {"family": "Hartiala", "given": "Jaana", "initials": "J", "orcid": "0000-0003-4883-9318", "researcher": {"href": "https://publications.scilifelab.se/researcher/f39400df71774cf8ae408eccbe34d981.json"}}, {"family": "Heydarpour", "given": "Mahyar", "initials": "M"}, {"family": "Pasterkamp", "given": "Gerard", "initials": "G"}, {"family": "Kotti", "given": "Salma", "initials": "S"}, {"family": "Kuukasj\u00e4rvi", "given": "Pekka", "initials": "P"}, {"family": "Lenzini", "given": "Petra A", "initials": "PA"}, {"family": "Levin", "given": "Daniel", "initials": "D"}, {"family": "Lyytik\u00e4inen", "given": "Leo-Pekka", "initials": "LP"}, {"family": "Muehlschlegel", "given": "Jochen D", "initials": "JD", "orcid": "0000-0002-6209-7253", "researcher": {"href": "https://publications.scilifelab.se/researcher/3211e8bb09c64d748cb153c358831d82.json"}}, {"family": "Nelson", "given": "Christopher P", "initials": "CP"}, {"family": "Nikus", "given": "Kjell", "initials": "K", "orcid": "0000-0002-9345-9851", "researcher": {"href": "https://publications.scilifelab.se/researcher/99b4b0a2893c42efbc24bed6370451ba.json"}}, {"family": "Pilbrow", "given": "Anna P", "initials": "AP", "orcid": "0000-0003-1949-9449", "researcher": {"href": "https://publications.scilifelab.se/researcher/b86a1225a68e403e806a07b42e96c991.json"}}, {"family": "Wilson Tang", "given": "W H", "initials": "WH", "orcid": "0000-0002-8335-735X", "researcher": {"href": "https://publications.scilifelab.se/researcher/5aab6a5657004a79aeda81c22a077268.json"}}, {"family": "van der Laan", "given": "Sander W", "initials": "SW", "orcid": "0000-0001-6888-1404", "researcher": {"href": "https://publications.scilifelab.se/researcher/9bd54ab413974b9096ff3d924f8b8eb6.json"}}, {"family": "van Setten", "given": "Jessica", "initials": "J"}, {"family": "Vilmundarson", "given": "Ragnar O", "initials": "RO"}, {"family": "Deanfield", "given": "John", "initials": "J"}, {"family": "Deloukas", "given": "Panos", "initials": "P", "orcid": "0000-0001-9251-070X", "researcher": {"href": "https://publications.scilifelab.se/researcher/eb59dbd2f2204d41b801c41188611a9e.json"}}, {"family": "Dudbridge", "given": "Frank", "initials": "F"}, {"family": "James", "given": "Stefan", "initials": "S"}, {"family": "Mordi", "given": "Ify R", "initials": "IR", "orcid": "0000-0002-2686-729X", "researcher": {"href": "https://publications.scilifelab.se/researcher/1081c6ce996d4f7e944be05db1a3e7c0.json"}}, {"family": "Teren", "given": "Andrej", "initials": "A"}, {"family": "Bergmeijer", "given": "Thomas O", "initials": "TO"}, {"family": "Body", "given": "Simon C", "initials": "SC"}, {"family": "Bots", "given": "Michiel", "initials": "M"}, {"family": "Burkhardt", "given": "Ralph", "initials": "R"}, {"family": "Cooper-DeHoff", "given": "Rhonda M", "initials": "RM"}, {"family": "Cresci", "given": "Sharon", "initials": "S"}, {"family": "Danchin", "given": "Nicolas", "initials": "N", "orcid": "0000-0001-9263-5051", "researcher": {"href": "https://publications.scilifelab.se/researcher/4c86ecd847894f7cb79f1f625881d60b.json"}}, {"family": "Doughty", "given": "Robert N", "initials": "RN"}, {"family": "Grobbee", "given": "Diederick E", "initials": "DE"}, {"family": "Hagstr\u00f6m", "given": "Emil", "initials": "E"}, {"family": "Hazen", "given": "Stanley L", "initials": "SL", "orcid": "0000-0001-7124-6639", "researcher": {"href": "https://publications.scilifelab.se/researcher/abce9cd916c94667a73bc348ede57a01.json"}}, {"family": "Held", "given": "Claes", "initials": "C"}, {"family": "Hoefer", "given": "Imo E", "initials": "IE"}, {"family": "Hovingh", "given": "G Kees", "initials": "GK"}, {"family": "Johnson", "given": "Julie A", "initials": "JA"}, {"family": "Kaczor", "given": "Marcin P", "initials": "MP"}, {"family": "K\u00e4h\u00f6nen", "given": "Mika", "initials": "M"}, {"family": "Klungel", "given": "Olaf H", "initials": "OH"}, {"family": "Laurikka", "given": "Jari O", "initials": "JO"}, {"family": "Lehtim\u00e4ki", "given": "Terho", "initials": "T"}, {"family": "Maitland-van der Zee", "given": "Anke H", "initials": "AH"}, {"family": "McPherson", "given": "Ruth", "initials": "R", "orcid": "0000-0002-9087-6107", "researcher": {"href": "https://publications.scilifelab.se/researcher/a563e055adb14878a8af46f235944082.json"}}, {"family": "Palmer", "given": "Colin N", "initials": "CN", "orcid": "0000-0002-6415-6560", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a0f019dcb7a453a84480953a5514dd5.json"}}, {"family": "Kraaijeveld", "given": "Adriaan O", "initials": "AO"}, {"family": "Pepine", "given": "Carl J", "initials": "CJ", "orcid": "0000-0002-6011-681X", "researcher": {"href": "https://publications.scilifelab.se/researcher/a3b76ccaa8a749bd83a0bc35a2d97557.json"}}, {"family": "Sanak", "given": "Marek", "initials": "M"}, {"family": "Sattar", "given": "Naveed", "initials": "N", "orcid": "0000-0002-1604-2593", "researcher": {"href": "https://publications.scilifelab.se/researcher/80fbc7cdcfc444acb066449f80f87181.json"}}, {"family": "Scholz", "given": "Markus", "initials": "M"}, {"family": "Simon", "given": "Tabassome", "initials": "T"}, {"family": "Spertus", "given": "John A", "initials": "JA"}, {"family": "Stewart", "given": "Alexandre F R", "initials": "AFR", "orcid": "0000-0003-2673-9164", "researcher": {"href": "https://publications.scilifelab.se/researcher/f6cd21cc0681418d845ab97d09f953c1.json"}}, {"family": "Szczeklik", "given": "Wojciech", "initials": "W"}, {"family": "Thiery", "given": "Joachim", "initials": "J"}, {"family": "Visseren", "given": "Frank L J", "initials": "FLJ"}, {"family": "Waltenberger", "given": "Johannes", "initials": "J", "orcid": "0000-0002-2417-9880", "researcher": {"href": "https://publications.scilifelab.se/researcher/a541817a1b1c49d79273fe61df23886e.json"}}, {"family": "Richards", "given": "A Mark", "initials": "AM"}, {"family": "Lang", "given": "Chim C", "initials": "CC"}, {"family": "Cameron", "given": "Vicky A", "initials": "VA"}, {"family": "\u00c5kerblom", "given": "Axel", "initials": "A"}, {"family": "Pare", "given": "Guillaume", "initials": "G", "orcid": "0000-0002-6795-4760", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e23d12d8f5340a79e86a293593c9598.json"}}, {"family": "M\u00e4rz", "given": "Winfried", "initials": "W"}, {"family": "Samani", "given": "Nilesh J", "initials": "NJ", "orcid": "0000-0002-3286-8133", "researcher": {"href": "https://publications.scilifelab.se/researcher/2227aaf274e8424f8408318f336f3bf1.json"}}, {"family": "Hingorani", "given": "Aroon D", "initials": "AD"}, {"family": "Ten Berg", "given": "Jurri\u00ebn M", "initials": "JM"}, {"family": "Wallentin", "given": "Lars", "initials": "L"}, {"family": "Asselbergs", "given": "Folkert W", "initials": "FW", "orcid": "0000-0002-1692-8669", "researcher": {"href": "https://publications.scilifelab.se/researcher/7037429ef1304bdaabd837d242b1e6f5.json"}}, {"family": "Patel", "given": "Riyaz S", "initials": "RS"}], "type": "journal article", "published": "2020-08-11", "journal": {"title": "Circulation", "issn": "1524-4539", "volume": "142", "issue": "6", "pages": "546-555", "issn-l": "0009-7322"}, "abstract": "Studies examining the role of factor V Leiden among patients at higher risk of atherothrombotic events, such as those with established coronary heart disease (CHD), are lacking. Given that coagulation is involved in the thrombus formation stage on atherosclerotic plaque rupture, we hypothesized that factor V Leiden may be a stronger risk factor for atherothrombotic events in patients with established CHD.\n\nWe performed an individual-level meta-analysis including 25 prospective studies (18 cohorts, 3 case-cohorts, 4 randomized trials) from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) consortium involving patients with established CHD at baseline. Participating studies genotyped factor V Leiden status and shared risk estimates for the outcomes of interest using a centrally developed statistical code with harmonized definitions across studies. Cox proportional hazards regression models were used to obtain age- and sex-adjusted estimates. The obtained estimates were pooled using fixed-effect meta-analysis. The primary outcome was composite of myocardial infarction and CHD death. Secondary outcomes included any stroke, ischemic stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality.\n\nThe studies included 69 681 individuals of whom 3190 (4.6%) were either heterozygous or homozygous (n=47) carriers of factor V Leiden. Median follow-up per study ranged from 1.0 to 10.6 years. A total of 20 studies with 61 147 participants and 6849 events contributed to analyses of the primary outcome. Factor V Leiden was not associated with the combined outcome of myocardial infarction and CHD death (hazard ratio, 1.03 [95% CI, 0.92-1.16]; I=28%; 2P-heterogeneity=0.12). Subgroup analysis according to baseline characteristics or strata of traditional cardiovascular risk factors did not show relevant differences. Similarly, risk estimates for the secondary outcomes including stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality were also close to identity.\n\nFactor V Leiden was not associated with increased risk of subsequent atherothrombotic events and mortality in high-risk participants with established and treated CHD. Routine assessment of factor V Leiden status is unlikely to improve atherothrombotic events risk stratification in this population.", "doi": "10.1161/CIRCULATIONAHA.119.045526", "pmid": "32654539", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7493828"}, {"db": "mid", "key": "NIHMS1610813"}], "notes": [], "created": "2020-08-04T14:50:04.900Z", "modified": "2021-11-10T12:49:19.053Z"}, {"entity": "publication", "iuid": "80bff0462f6c4a8b87640fd9aec16812", "links": {"self": {"href": "https://publications.scilifelab.se/publication/80bff0462f6c4a8b87640fd9aec16812.json"}, "display": {"href": "https://publications.scilifelab.se/publication/80bff0462f6c4a8b87640fd9aec16812"}}, "title": "Proteomic Biomarkers for Incident Aortic Stenosis Requiring Valvular Replacement.", "authors": [{"family": "Ljungberg", "given": "Johan", "initials": "J"}, {"family": "Janiec", "given": "Mikael", "initials": "M"}, {"family": "Bergdahl", "given": "Ingvar A", "initials": "IA"}, {"family": "Holmgren", "given": "Anders", "initials": "A"}, {"family": "Hultdin", "given": "Johan", "initials": "J"}, {"family": "Johansson", "given": "Bengt", "initials": "B"}, {"family": "N\u00e4slund", "given": "Ulf", "initials": "U"}, {"family": "Siegbahn", "given": "Agneta", "initials": "A"}, {"family": "Fall", "given": "Tove", "initials": "T"}, {"family": "S\u00f6derberg", "given": "Stefan", "initials": "S"}], "type": "journal article", "published": "2018-08-07", "journal": {"title": "Circulation", "issn": "1524-4539", "issn-l": "0009-7322", "volume": "138", "issue": "6", "pages": "590-599"}, "abstract": "Aortic valve stenosis (AS) is the most common indication for cardiac valve surgery; untreated AS is linked to high mortality. The etiological background of AS is unknown. Previous human studies were typically based on case-control studies. Biomarkers identified in prospective studies could lead to novel mechanistic insights.\n\nWithin a large population survey with blood samples obtained at baseline, 334 patients were identified who later underwent surgery for AS (median age [interquartile range], 59.9 [10.4] years at survey and 68.3 [12.7] at surgery; 48% female). For each case, 2 matched referents were allocated. Plasma was analyzed with the multiplex proximity extension assay for screening of 92 cardiovascular candidate proteins. Conditional logistic regression models were used to assess associations between each protein and AS, with correction for multiple testing. A separate set of 106 additional cases with 212 matched referents was used in a validation study.\n\nSix proteins (growth differentiation factor 15, galectin-4, von Willebrand factor, interleukin 17 receptor A, transferrin receptor protein 1, and proprotein convertase subtilisin/kexin type 9) were associated with case status in the discovery cohort; odds ratios ranged from 1.25 to 1.37 per SD increase in the protein signal. Adjusting the multivariable models for classical cardiovascular risk factors at baseline yielded similar results. Subanalyses of case-referent triplets (n=133) who showed no visible coronary artery disease at the time of surgery in the index person supported associations between AS and growth differentiation factor 15 (odds ratio, 1.40; 95% confidence interval, 1.10-1.78) and galectin-4 (odds ratio, 1.27; 95% confidence interval, 1.02-1.59), but these associations were attenuated after excluding individuals who donated blood samples within 5 years before surgery. In triplets (n=201), which included index individuals with concurrent coronary artery disease at the time of surgery, all 6 proteins were robustly associated with case status in all sensitivity analyses. In the validation study, the association of all but 1 (interleukin 17 receptor A) of these proteins were replicated in patients with AS with concurrent coronary artery disease but not in patients with AS without coronary artery disease.\n\nWe provide evidence that 5 proteins were altered years before AS surgery and that the associations seem to be driven by concurrent atherosclerotic disease.", "doi": "10.1161/CIRCULATIONAHA.117.030414", "pmid": "29487139", "labels": {"Clinical Biomarkers": "Service", "PLA and Single Cell Proteomics": "Service", "Affinity Proteomics Uppsala": "Service"}, "xrefs": [{"db": "pii", "key": "CIRCULATIONAHA.117.030414"}], "notes": [], "created": "2020-01-23T16:03:58.900Z", "modified": "2023-04-14T13:56:03.408Z"}, {"entity": "publication", "iuid": "f5818ee56db54974b5c5af9fad41848c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f5818ee56db54974b5c5af9fad41848c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f5818ee56db54974b5c5af9fad41848c"}}, "title": "Growth differentiation factor 15, a marker of oxidative stress and inflammation, for risk assessment in patients with atrial fibrillation: insights from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial.", "authors": [{"family": "Wallentin", "given": "Lars", "initials": "L"}, {"family": "Hijazi", "given": "Ziad", "initials": "Z"}, {"family": "Andersson", "given": "Ulrika", "initials": "U"}, {"family": "Alexander", "given": "John H", "initials": "JH"}, {"family": "De Caterina", "given": "Raffaele", "initials": "R"}, {"family": "Hanna", "given": "Michael", "initials": "M"}, {"family": "Horowitz", "given": "John D", "initials": "JD"}, {"family": "Hylek", "given": "Elaine M", "initials": "EM"}, {"family": "Lopes", "given": "Renato D", "initials": "RD"}, {"family": "Asberg", "given": "Signild", "initials": "S"}, {"family": "Granger", "given": "Christopher B", "initials": "CB"}, {"family": "Siegbahn", "given": "Agneta", "initials": "A"}, {"family": "ARISTOTLE Investigators", "given": "", "initials": ""}], "type": "journal article", "published": "2014-11-18", "journal": {"title": "Circulation", "issn": "1524-4539", "issn-l": "0009-7322", "volume": "130", "issue": "21", "pages": "1847-1858"}, "abstract": "Growth differentiation factor 15 (GDF-15), high-sensitivity troponin, and N-terminal pro-brain natriuretic peptide levels are predictive of death and cardiovascular events in healthy elderly subjects, patients with acute coronary syndrome, and patients with heart failure. High-sensitivity troponin I and N-terminal pro-brain natriuretic peptide are also prognostic in patients with atrial fibrillation. We evaluated the prognostic value of GDF-15 alone and in addition to clinical characteristics and other biomarkers in patients with atrial fibrillation.\n\nThe Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial randomized 18 201 patients with atrial fibrillation to apixaban or warfarin. Biomarkers were measured at randomization in 14 798 patients. Efficacy and safety outcomes during 1.9 years of follow-up were compared across quartiles of GDF-15 by use of Cox analyses adjusted for clinical characteristics, randomized treatment, and other biomarkers. The GDF-15 level showed a median of 1383 ng/L (interquartile range, 977-2052 ng/L). Annual rates of stroke or systemic embolism ranged from 0.9% to 2.03% (P<0.001); of major bleeding, from 1.22% to 4.53% (P<0.001); and of mortality, from 1.34% to 7.19% (P<0.001) in the lowest compared with the highest GDF-15 quartile. The prognostic information provided by GDF-15 was independent of clinical characteristics and clinical risk scores. Adjustment for the other cardiac biomarkers attenuated the prognostic value for stroke, whereas the prognostic value for mortality and major bleeding remained. Apixaban consistently reduced stroke, mortality, and bleeding, regardless of GDF-15 levels.\n\nGDF-15 is a risk factor for major bleeding, mortality, and stroke in atrial fibrillation. The prognostic value for major bleeding and death remained even in the presence of N-terminal pro-brain natriuretic peptide and high-sensitivity troponin I.\n\nhttp://www.clinicaltrials.gov. Unique identifier: NCT00412984.", "doi": "10.1161/CIRCULATIONAHA.114.011204", "pmid": "25294786", "labels": {"Clinical Biomarkers": "", "PLA and Single Cell Proteomics": "Service", "Affinity Proteomics Uppsala": "Technology development"}, "xrefs": [{"db": "pii", "key": "CIRCULATIONAHA.114.011204"}, {"db": "ClinicalTrials.gov", "key": "NCT00412984"}], "notes": [], "created": "2017-05-04T14:56:53.902Z", "modified": "2023-04-14T13:56:27.177Z"}, {"entity": "publication", "iuid": "96d1d883dc3749999572787646fb4357", "links": {"self": {"href": "https://publications.scilifelab.se/publication/96d1d883dc3749999572787646fb4357.json"}, "display": {"href": "https://publications.scilifelab.se/publication/96d1d883dc3749999572787646fb4357"}}, "title": "Multiethnic meta-analysis of genome-wide association studies in >100 000 subjects identifies 23 fibrinogen-associated Loci but no strong evidence of a causal association between circulating fibrinogen and cardiovascular disease.", "authors": [{"family": "Sabater-Lleal", "given": "Maria", "initials": "M"}, {"family": "Huang", "given": "Jie", "initials": "J"}, {"family": "Chasman", "given": "Daniel", "initials": "D"}, {"family": "Naitza", "given": "Silvia", "initials": "S"}, {"family": "Dehghan", "given": "Abbas", "initials": "A"}, {"family": "Johnson", "given": "Andrew D", "initials": "AD"}, {"family": "Teumer", "given": "Alexander", "initials": "A"}, {"family": "Reiner", "given": "Alex P", "initials": "AP"}, {"family": "Folkersen", "given": "Lasse", "initials": "L"}, {"family": "Basu", "given": "Saonli", "initials": "S"}, {"family": "Rudnicka", "given": "Alicja R", "initials": "AR"}, {"family": "Trompet", "given": "Stella", "initials": "S"}, {"family": "M\u00e4larstig", "given": "Anders", "initials": "A"}, {"family": "Baumert", "given": "Jens", "initials": "J"}, {"family": "Bis", "given": "Joshua C", "initials": "JC"}, {"family": "Guo", "given": "Xiuqing", "initials": "X"}, {"family": "Hottenga", "given": "Jouke J", "initials": "JJ"}, {"family": "Shin", "given": "So-Youn", "initials": "SY"}, {"family": "Lopez", "given": "Lorna M", "initials": "LM"}, {"family": "Lahti", "given": "Jari", "initials": "J"}, {"family": "Tanaka", "given": "Toshiko", "initials": "T"}, {"family": "Yanek", "given": "Lisa R", "initials": "LR"}, {"family": "Oudot-Mellakh", "given": "Tiphaine", "initials": "T"}, {"family": "Wilson", "given": "James F", "initials": "JF"}, {"family": "Navarro", "given": "Pau", "initials": "P"}, {"family": "Huffman", "given": "Jennifer E", "initials": "JE"}, {"family": "Zemunik", "given": "Tatijana", "initials": "T"}, {"family": "Redline", "given": "Susan", "initials": "S"}, {"family": "Mehra", "given": "Reena", "initials": "R"}, {"family": "Pulanic", "given": "Drazen", "initials": "D"}, {"family": "Rudan", "given": "Igor", "initials": "I"}, {"family": "Wright", "given": "Alan F", "initials": "AF"}, {"family": "Kolcic", "given": "Ivana", "initials": "I"}, {"family": "Polasek", "given": "Ozren", "initials": "O"}, {"family": "Wild", "given": "Sarah H", "initials": "SH"}, {"family": "Campbell", "given": "Harry", "initials": "H"}, {"family": "Curb", "given": "J David", "initials": "JD"}, {"family": "Wallace", "given": "Robert", "initials": "R"}, {"family": "Liu", "given": "Simin", "initials": "S"}, {"family": "Eaton", "given": "Charles B", "initials": "CB"}, {"family": "Becker", "given": "Diane M", "initials": "DM"}, {"family": "Becker", "given": "Lewis C", "initials": "LC"}, {"family": "Bandinelli", "given": "Stefania", "initials": "S"}, {"family": "R\u00e4ikk\u00f6nen", "given": "Katri", "initials": "K"}, {"family": "Widen", "given": "Elisabeth", "initials": "E"}, {"family": "Palotie", "given": "Aarno", "initials": "A"}, {"family": "Fornage", "given": "Myriam", "initials": "M"}, {"family": "Green", "given": "David", "initials": "D"}, {"family": "Gross", "given": "Myron", "initials": "M"}, {"family": "Davies", "given": "Gail", "initials": "G"}, {"family": "Harris", "given": "Sarah E", "initials": "SE"}, {"family": "Liewald", "given": "David C", "initials": "DC"}, {"family": "Starr", "given": "John M", "initials": "JM"}, {"family": "Williams", "given": "Frances M K", "initials": "FM"}, {"family": "Grant", "given": "Peter J", "initials": "PJ"}, {"family": "Spector", "given": "Timothy D", "initials": "TD"}, {"family": "Strawbridge", "given": "Rona J", "initials": "RJ"}, {"family": "Silveira", "given": "Angela", "initials": "A"}, {"family": "Sennblad", "given": "Bengt", "initials": "B"}, {"family": "Rivadeneira", "given": "Fernando", "initials": "F"}, {"family": "Uitterlinden", "given": "Andre G", "initials": "AG"}, {"family": "Franco", "given": "Oscar H", "initials": "OH"}, {"family": "Hofman", "given": "Albert", "initials": "A"}, {"family": "van Dongen", "given": "Jenny", "initials": "J"}, {"family": "Willemsen", "given": "Gonneke", "initials": "G"}, {"family": "Boomsma", "given": "Dorret I", "initials": "DI"}, {"family": "Yao", "given": "Jie", "initials": "J"}, {"family": "Swords Jenny", "given": "Nancy", "initials": "N"}, {"family": "Haritunians", "given": "Talin", "initials": "T"}, {"family": "McKnight", "given": "Barbara", "initials": "B"}, {"family": "Lumley", "given": "Thomas", "initials": "T"}, {"family": "Taylor", "given": "Kent D", "initials": "KD"}, {"family": "Rotter", "given": "Jerome I", "initials": "JI"}, {"family": "Psaty", "given": "Bruce M", "initials": "BM"}, {"family": "Peters", "given": "Annette", "initials": "A"}, {"family": "Gieger", "given": "Christian", "initials": "C"}, {"family": "Illig", "given": "Thomas", "initials": "T"}, {"family": "Grotevendt", "given": "Anne", "initials": "A"}, {"family": "Homuth", "given": "Georg", "initials": "G"}, {"family": "V\u00f6lzke", "given": "Henry", "initials": "H"}, {"family": "Kocher", "given": "Thomas", "initials": "T"}, {"family": "Goel", "given": "Anuj", "initials": "A"}, {"family": "Franzosi", "given": "Maria Grazia", "initials": "MG"}, {"family": "Seedorf", "given": "Udo", "initials": "U"}, {"family": "Clarke", "given": "Robert", "initials": "R"}, {"family": "Steri", "given": "Maristella", "initials": "M"}, {"family": "Tarasov", "given": "Kirill V", "initials": "KV"}, {"family": "Sanna", "given": "Serena", "initials": "S"}, {"family": "Schlessinger", "given": "David", "initials": "D"}, {"family": "Stott", "given": "David J", "initials": "DJ"}, {"family": "Sattar", "given": "Naveed", "initials": "N"}, {"family": "Buckley", "given": "Brendan M", "initials": "BM"}, {"family": "Rumley", "given": "Ann", "initials": "A"}, {"family": "Lowe", "given": "Gordon D", "initials": "GD"}, {"family": "McArdle", "given": "Wendy L", "initials": "WL"}, {"family": "Chen", "given": "Ming-Huei", "initials": "MH"}, {"family": "Tofler", "given": "Geoffrey H", "initials": "GH"}, {"family": "Song", "given": "Jaejoon", "initials": "J"}, {"family": "Boerwinkle", "given": "Eric", "initials": "E"}, {"family": "Folsom", "given": "Aaron R", "initials": "AR"}, {"family": "Rose", "given": "Lynda M", "initials": "LM"}, {"family": "Franco-Cereceda", "given": "Anders", "initials": "A"}, {"family": "Teichert", "given": "Martina", "initials": "M"}, {"family": "Ikram", "given": "M Arfan", "initials": "MA"}, {"family": "Mosley", "given": "Thomas H", "initials": "TH"}, {"family": "Bevan", "given": "Steve", "initials": "S"}, {"family": "Dichgans", "given": "Martin", "initials": "M"}, {"family": "Rothwell", "given": "Peter M", "initials": "PM"}, {"family": "Sudlow", "given": "Cathie L M", "initials": "CL"}, {"family": "Hopewell", "given": "Jemma C", "initials": "JC"}, {"family": "Chambers", "given": "John C", "initials": "JC"}, {"family": "Saleheen", "given": "Danish", "initials": "D"}, {"family": "Kooner", "given": "Jaspal S", "initials": "JS"}, {"family": "Danesh", "given": "John", "initials": "J"}, {"family": "Nelson", "given": "Christopher P", "initials": "CP"}, {"family": "Erdmann", "given": "Jeanette", "initials": "J"}, {"family": "Reilly", "given": "Muredach P", "initials": "MP"}, {"family": "Kathiresan", "given": "Sekar", "initials": "S"}, {"family": "Schunkert", "given": "Heribert", "initials": "H"}, {"family": "Morange", "given": "Pierre-Emmanuel", "initials": "PE"}, {"family": "Ferrucci", "given": "Luigi", "initials": "L"}, {"family": "Eriksson", "given": "Johan G", "initials": "JG"}, {"family": "Jacobs", "given": "David", "initials": "D"}, {"family": "Deary", "given": "Ian J", "initials": "IJ"}, {"family": "Soranzo", "given": "Nicole", "initials": "N"}, {"family": "Witteman", "given": "Jacqueline C M", "initials": "JC"}, {"family": "de Geus", "given": "Eco J C", "initials": "EJ"}, {"family": "Tracy", "given": "Russell P", "initials": "RP"}, {"family": "Hayward", "given": "Caroline", "initials": "C"}, {"family": "Koenig", "given": "Wolfgang", "initials": "W"}, {"family": "Cucca", "given": "Francesco", "initials": "F"}, {"family": "Jukema", "given": "J Wouter", "initials": "JW"}, {"family": "Eriksson", "given": "Per", "initials": "P"}, {"family": "Seshadri", "given": "Sudha", "initials": "S"}, {"family": "Markus", "given": "Hugh S", "initials": "HS"}, {"family": "Watkins", "given": "Hugh", "initials": "H"}, {"family": "Samani", "given": "Nilesh J", "initials": "NJ"}, {"family": "VTE Consortium", "given": null, "initials": null}, {"family": "STROKE Consortium", "given": null, "initials": null}, {"family": "Wellcome Trust Case Control Consortium 2 (WTCCC2)", "given": null, "initials": null}, {"family": "C4D Consortium", "given": null, "initials": null}, {"family": "CARDIoGRAM Consortium", "given": null, "initials": null}, {"family": "Wallaschofski", "given": "Henri", "initials": "H"}, {"family": "Smith", "given": "Nicholas L", "initials": "NL"}, {"family": "Tregouet", "given": "David", "initials": "D"}, {"family": "Ridker", "given": "Paul M", "initials": "PM"}, {"family": "Tang", "given": "Weihong", "initials": "W"}, {"family": "Strachan", "given": "David P", "initials": "DP"}, {"family": "Hamsten", "given": "Anders", "initials": "A"}, {"family": "O'Donnell", "given": "Christopher J", "initials": "CJ"}], "type": "journal article", "published": "2013-09-17", "journal": {"volume": "128", "issn": "1524-4539", "issue": "12", "pages": "1310-1324", "title": "Circulation", "issn-l": "0009-7322"}, "abstract": "Estimates of the heritability of plasma fibrinogen concentration, an established predictor of cardiovascular disease, range from 34% to 50%. Genetic variants so far identified by genome-wide association studies explain only a small proportion (<2%) of its variation.\n\nWe conducted a meta-analysis of 28 genome-wide association studies including >90 000 subjects of European ancestry, the first genome-wide association meta-analysis of fibrinogen levels in 7 studies in blacks totaling 8289 samples, and a genome-wide association study in Hispanics totaling 1366 samples. Evaluation for association of single-nucleotide polymorphisms with clinical outcomes included a total of 40 695 cases and 85 582 controls for coronary artery disease, 4752 cases and 24 030 controls for stroke, and 3208 cases and 46 167 controls for venous thromboembolism. Overall, we identified 24 genome-wide significant (P<5\u00d710(-8)) independent signals in 23 loci, including 15 novel associations, together accounting for 3.7% of plasma fibrinogen variation. Gene-set enrichment analysis highlighted key roles in fibrinogen regulation for the 3 structural fibrinogen genes and pathways related to inflammation, adipocytokines, and thyrotrophin-releasing hormone signaling. Whereas lead single-nucleotide polymorphisms in a few loci were significantly associated with coronary artery disease, the combined effect of all 24 fibrinogen-associated lead single-nucleotide polymorphisms was not significant for coronary artery disease, stroke, or venous thromboembolism.\n\nWe identify 23 robustly associated fibrinogen loci, 15 of which are new. Clinical outcome analysis of these loci does not support a causal relationship between circulating levels of fibrinogen and coronary artery disease, stroke, or venous thromboembolism.", "doi": "10.1161/CIRCULATIONAHA.113.002251", "pmid": "23969696", "labels": {"National Genomics Infrastructure": null, "NGI Stockholm (Genomics Applications)": null, "NGI Stockholm (Genomics Production)": null}, "xrefs": [{"db": "pii", "key": "CIRCULATIONAHA.113.002251"}, {"db": "pmc", "key": "PMC3842025"}, {"db": "mid", "key": "NIHMS518819"}], "notes": [], "created": "2017-05-04T14:57:50.942Z", "modified": "2020-01-21T13:56:03.878Z"}, {"entity": "publication", "iuid": "95abadec9dcf4a13b3ae92cd0dadc428", "links": {"self": {"href": "https://publications.scilifelab.se/publication/95abadec9dcf4a13b3ae92cd0dadc428.json"}, "display": {"href": "https://publications.scilifelab.se/publication/95abadec9dcf4a13b3ae92cd0dadc428"}}, "title": "Genetic determinants of dabigatran plasma levels and their relation to bleeding.", "authors": [{"family": "Par\u00e9", "given": "Guillaume", "initials": "G"}, {"family": "Eriksson", "given": "Niclas", "initials": "N"}, {"family": "Lehr", "given": "Thorsten", "initials": "T"}, {"family": "Connolly", "given": "Stuart", "initials": "S"}, {"family": "Eikelboom", "given": "John", "initials": "J"}, {"family": "Ezekowitz", "given": "Michael D", "initials": "MD"}, {"family": "Axelsson", "given": "Tomas", "initials": "T"}, {"family": "Haertter", "given": "Sebastian", "initials": "S"}, {"family": "Oldgren", "given": "Jonas", "initials": "J"}, {"family": "Reilly", "given": "Paul", "initials": "P"}, {"family": "Siegbahn", "given": "Agneta", "initials": "A"}, {"family": "Syvanen", "given": "Ann-Christine", "initials": "AC", "orcid": "0000-0002-9681-9146", "researcher": {"href": "https://publications.scilifelab.se/researcher/f7012e35025543379380cb90efd71243.json"}}, {"family": "Wadelius", "given": "Claes", "initials": "C"}, {"family": "Wadelius", "given": "Mia", "initials": "M"}, {"family": "Zimdahl-Gelling", "given": "Heike", "initials": "H"}, {"family": "Yusuf", "given": "Salim", "initials": "S"}, {"family": "Wallentin", "given": "Lars", "initials": "L"}], "type": "journal article", "published": "2013-04-02", "journal": {"volume": "127", "issn": "1524-4539", "issue": "13", "pages": "1404-1412", "title": "Circulation", "issn-l": "0009-7322"}, "abstract": "Fixed-dose unmonitored treatment with dabigatran etexilate is effective and has a favorable safety profile in the prevention of stroke in atrial fibrillation patients compared with warfarin. We hypothesized that genetic variants could contribute to interindividual variability in blood concentrations of the active metabolite of dabigatran etexilate and influence the safety and efficacy of dabigatran.\n\nWe successfully conducted a genome-wide association study in 2944 Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) participants. The CES1 single-nucleotide polymorphism rs2244613 was associated with trough concentrations, and the ABCB1 single-nucleotide polymorphism rs4148738 and the CES1 single-nucleotide polymorphism rs8192935 were associated with peak concentrations at genome-wide significance (P<9\u00d710(-8)) with a gene-dose effect. Each minor allele of the CES1 single-nucleotide polymorphism rs2244613 was associated with lower trough concentrations (15% decrease per allele; 95% confidence interval, 10-19; P=1.2\u00d710(-8)) and a lower risk of any bleeding (odds ratio, 0.67; 95% confidence interval, 0.55-0.82; P=7\u00d710(-5)) in dabigatran-treated participants, with a consistent but nonsignificant lower risk of major bleeding (odds ratio, 0.66; 95% confidence interval, 0.43-1.01). The interaction between treatment (warfarin versus all dabigatran) and carrier status was statistically significant (P=0.002), with carriers having less bleeding with dabigatran than warfarin (hazard ratio, 0.59; 95% confidence interval, 0.46-0.76; P=5.2\u00d710(-)5) in contrast to no difference in noncarriers (hazard ratio, 0.96; 95% confidence interval, 0.81-1.14; P=0.65). There was no association with ischemic events, and neither rs4148738 nor rs8192935 was associated with bleeding or ischemic events.\n\nGenome-wide association analysis identified that carriage of the CES1 rs2244613 minor allele occurred in 32.8% of patients in RE-LY and was associated with lower exposure to active dabigatran metabolite. The presence of the polymorphism was associated with a lower risk of bleeding.\n\nURL: http://www.clinicaltrials.gov. Unique identifier: NCT00262600.", "doi": "10.1161/CIRCULATIONAHA.112.001233", "pmid": "23467860", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (SNP&SEQ Technology Platform)": null}, "xrefs": [{"db": "pii", "key": "CIRCULATIONAHA.112.001233"}, {"db": "ClinicalTrials.gov", "key": "NCT00262600"}], "notes": [], "created": "2017-05-04T15:01:15.922Z", "modified": "2021-07-07T15:11:02.603Z"}, {"entity": "publication", "iuid": "fcbf14320d5940089c81f815bf63a72e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/fcbf14320d5940089c81f815bf63a72e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/fcbf14320d5940089c81f815bf63a72e"}}, "title": "Novel associations of multiple genetic loci with plasma levels of factor VII, factor VIII, and von Willebrand factor: The CHARGE (Cohorts for Heart and Aging Research in Genome Epidemiology) Consortium.", "authors": [{"family": "Smith", "given": "Nicholas L", "initials": "NL"}, {"family": "Chen", "given": "Ming-Huei", "initials": "MH"}, {"family": "Dehghan", "given": "Abbas", "initials": "A"}, {"family": "Strachan", "given": "David P", "initials": "DP"}, {"family": "Basu", "given": "Saonli", "initials": "S"}, {"family": "Soranzo", "given": "Nicole", "initials": "N"}, {"family": "Hayward", "given": "Caroline", "initials": "C"}, {"family": "Rudan", "given": "Igor", "initials": "I"}, {"family": "Sabater-Lleal", "given": "Maria", "initials": "M"}, {"family": "Bis", "given": "Joshua C", "initials": "JC"}, {"family": "de Maat", "given": "Moniek P M", "initials": "MP"}, {"family": "Rumley", "given": "Ann", "initials": "A"}, {"family": "Kong", "given": "Xiaoxiao", "initials": "X"}, {"family": "Yang", "given": "Qiong", "initials": "Q"}, {"family": "Williams", "given": "Frances M K", "initials": "FM"}, {"family": "Vitart", "given": "Veronique", "initials": "V"}, {"family": "Campbell", "given": "Harry", "initials": "H"}, {"family": "M\u00e4larstig", "given": "Anders", "initials": "A"}, {"family": "Wiggins", "given": "Kerri L", "initials": "KL"}, {"family": "Van Duijn", "given": "Cornelia M", "initials": "CM"}, {"family": "McArdle", "given": "Wendy L", "initials": "WL"}, {"family": "Pankow", "given": "James S", "initials": "JS"}, {"family": "Johnson", "given": "Andrew D", "initials": "AD"}, {"family": "Silveira", "given": "Angela", "initials": "A"}, {"family": "McKnight", "given": "Barbara", "initials": "B"}, {"family": "Uitterlinden", "given": "Andre G", "initials": "AG"}, {"family": "Wellcome Trust Case Control Consortium;", "given": null, "initials": null}, {"family": "Aleksic", "given": "Nena", "initials": "N"}, {"family": "Meigs", "given": "James B", "initials": "JB"}, {"family": "Peters", "given": "Annette", "initials": "A"}, {"family": "Koenig", "given": "Wolfgang", "initials": "W"}, {"family": "Cushman", "given": "Mary", "initials": "M"}, {"family": "Kathiresan", "given": "Sekar", "initials": "S"}, {"family": "Rotter", "given": "Jerome I", "initials": "JI"}, {"family": "Bovill", "given": "Edwin G", "initials": "EG"}, {"family": "Hofman", "given": "Albert", "initials": "A"}, {"family": "Boerwinkle", "given": "Eric", "initials": "E"}, {"family": "Tofler", "given": "Geoffrey H", "initials": "GH"}, {"family": "Peden", "given": "John F", "initials": "JF"}, {"family": "Psaty", "given": "Bruce M", "initials": "BM"}, {"family": "Leebeek", "given": "Frank", "initials": "F"}, {"family": "Folsom", "given": "Aaron R", "initials": "AR"}, {"family": "Larson", "given": "Martin G", "initials": "MG"}, {"family": "Spector", "given": "Timothy D", "initials": "TD"}, {"family": "Wright", "given": "Alan F", "initials": "AF"}, {"family": "Wilson", "given": "James F", "initials": "JF"}, {"family": "Hamsten", "given": "Anders", "initials": "A"}, {"family": "Lumley", "given": "Thomas", "initials": "T"}, {"family": "Witteman", "given": "Jacqueline C M", "initials": "JC"}, {"family": "Tang", "given": "Weihong", "initials": "W"}, {"family": "O'Donnell", "given": "Christopher J", "initials": "CJ"}], "type": "journal article", "published": "2010-03-30", "journal": {"volume": "121", "issn": "1524-4539", "issue": "12", "pages": "1382-1392", "title": "Circulation", "issn-l": "0009-7322"}, "abstract": "Plasma levels of coagulation factors VII (FVII), VIII (FVIII), and von Willebrand factor (vWF) influence risk of hemorrhage and thrombosis. We conducted genome-wide association studies to identify new loci associated with plasma levels.\n\nThe setting of the study included 5 community-based studies for discovery comprising 23 608 European-ancestry participants: Atherosclerosis Risk In Communities Study, Cardiovascular Health Study, British 1958 Birth Cohort, Framingham Heart Study, and Rotterdam Study. All subjects had genome-wide single-nucleotide polymorphism (SNP) scans and at least 1 phenotype measured: FVII activity/antigen, FVIII activity, and vWF antigen. Each study used its genotype data to impute to HapMap SNPs and independently conducted association analyses of hemostasis measures using an additive genetic model. Study findings were combined by meta-analysis. Replication was conducted in 7604 participants not in the discovery cohort. For FVII, 305 SNPs exceeded the genome-wide significance threshold of 5.0x10(-8) and comprised 5 loci on 5 chromosomes: 2p23 (smallest P value 6.2x10(-24)), 4q25 (3.6x10(-12)), 11q12 (2.0x10(-10)), 13q34 (9.0x10(-259)), and 20q11.2 (5.7x10(-37)). Loci were within or near genes, including 4 new candidate genes and F7 (13q34). For vWF, 400 SNPs exceeded the threshold and marked 8 loci on 6 chromosomes: 6q24 (1.2x10(-22)), 8p21 (1.3x10(-16)), 9q34 (<5.0x10(-324)), 12p13 (1.7x10(-32)), 12q23 (7.3x10(-10)), 12q24.3 (3.8x10(-11)), 14q32 (2.3x10(-10)), and 19p13.2 (1.3x10(-9)). All loci were within genes, including 6 new candidate genes, as well as ABO (9q34) and VWF (12p13). For FVIII, 5 loci were identified and overlapped vWF findings. Nine of the 10 new findings were replicated.\n\nNew genetic associations were discovered outside previously known biological pathways and may point to novel prevention and treatment targets of hemostasis disorders.", "doi": "10.1161/CIRCULATIONAHA.109.869156", "pmid": "20231535", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (SNP&SEQ Technology Platform)": null}, "xrefs": [{"db": "pii", "key": "CIRCULATIONAHA.109.869156"}, {"db": "pmc", "key": "PMC2861278"}, {"db": "mid", "key": "NIHMS189970"}], "notes": [], "created": "2017-05-04T15:00:28.878Z", "modified": "2020-01-21T13:56:06.495Z"}], "created": "2017-05-09T09:12:17.865Z", "modified": "2020-11-27T13:14:04.523Z"}