{"entity": "journal", "iuid": "edb60370025049a992e44d9524261f07", "timestamp": "2026-07-20T01:32:15.887Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/Circ.%20Res..json"}, "display": {"href": "https://publications.scilifelab.se/journal/Circ.%20Res."}}, "title": "Circ. Res.", "issn": "1524-4571", "issn-l": "0009-7330", "publications_count": 6, "publications": [{"entity": "publication", "iuid": "e3d69bb4a276419495bce013353a7d00", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e3d69bb4a276419495bce013353a7d00.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e3d69bb4a276419495bce013353a7d00"}}, "title": "Single-Cell Analysis of Blood-Brain Barrier Response to Pericyte Loss.", "authors": [{"family": "M\u00e4e", "given": "Maarja A", "initials": "MA"}, {"family": "He", "given": "Liqun", "initials": "L"}, {"family": "Nordling", "given": "Sofia", "initials": "S"}, {"family": "Vazquez-Liebanas", "given": "Elisa", "initials": "E"}, {"family": "Nahar", "given": "Khayrun", "initials": "K"}, {"family": "Jung", "given": "Bongnam", "initials": "B"}, {"family": "Li", "given": "Xidan", "initials": "X"}, {"family": "Tan", "given": "Bryan C", "initials": "BC"}, {"family": "Chin Foo", "given": "Juat", "initials": "J"}, {"family": "Cazenave-Gassiot", "given": "Amaury", "initials": "A"}, {"family": "Wenk", "given": "Markus R", "initials": "MR"}, {"family": "Zarb", "given": "Yvette", "initials": "Y"}, {"family": "Lavina", "given": "Barbara", "initials": "B"}, {"family": "Quaggin", "given": "Susan E", "initials": "SE"}, {"family": "Jeansson", "given": "Marie", "initials": "M"}, {"family": "Gu", "given": "Chengua", "initials": "C"}, {"family": "Silver", "given": "David L", "initials": "DL"}, {"family": "Vanlandewijck", "given": "Michael", "initials": "M"}, {"family": "Butcher", "given": "Eugene C", "initials": "EC"}, {"family": "Keller", "given": "Annika", "initials": "A"}, {"family": "Betsholtz", "given": "Christer", "initials": "C"}], "type": "journal article", "published": "2021-02-19", "journal": {"title": "Circ. Res.", "issn": "1524-4571", "volume": "128", "issue": "4", "pages": "e46-e62", "issn-l": "0009-7330"}, "abstract": "Pericytes are capillary mural cells playing a role in stabilizing newly formed blood vessels during development and tissue repair. Loss of pericytes has been described in several brain disorders, and genetically induced pericyte deficiency in the brain leads to increased macromolecular leakage across the blood-brain barrier (BBB). However, the molecular details of the endothelial response to pericyte deficiency remain elusive.\n\nTo map the transcriptional changes in brain endothelial cells resulting from lack of pericyte contact at single-cell level and to correlate them with regional heterogeneities in BBB function and vascular phenotype.\n\nWe reveal transcriptional, morphological, and functional consequences of pericyte absence for brain endothelial cells using a combination of methodologies, including single-cell RNA sequencing, tracer analyses, and immunofluorescent detection of protein expression in pericyte-deficient adult Pdgfbret/ret mice. We find that endothelial cells without pericyte contact retain a general BBB-specific gene expression profile, however, they acquire a venous-shifted molecular pattern and become transformed regarding the expression of numerous growth factors and regulatory proteins. Adult Pdgfbret/ret brains display ongoing angiogenic sprouting without concomitant cell proliferation providing unique insights into the endothelial tip cell transcriptome. We also reveal heterogeneous modes of pericyte-deficient BBB impairment, where hotspot leakage sites display arteriolar-shifted identity and pinpoint putative BBB regulators. By testing the causal involvement of some of these using reverse genetics, we uncover a reinforcing role for angiopoietin 2 at the BBB.\n\nBy elucidating the complexity of endothelial response to pericyte deficiency at cellular resolution, our study provides insight into the importance of brain pericytes for endothelial arterio-venous zonation, angiogenic quiescence, and a limited set of BBB functions. The BBB-reinforcing role of ANGPT2 (angiopoietin 2) is paradoxical given its wider role as TIE2 (TEK receptor tyrosine kinase) receptor antagonist and may suggest a unique and context-dependent function of ANGPT2 in the brain.", "doi": "10.1161/CIRCRESAHA.120.317473", "pmid": "33375813", "labels": {"Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [], "notes": [], "created": "2022-11-09T16:00:05.938Z", "modified": "2024-01-16T13:48:40.637Z"}, {"entity": "publication", "iuid": "801a1c8a83fa4b0183e5729b84f7a003", "links": {"self": {"href": "https://publications.scilifelab.se/publication/801a1c8a83fa4b0183e5729b84f7a003.json"}, "display": {"href": "https://publications.scilifelab.se/publication/801a1c8a83fa4b0183e5729b84f7a003"}}, "title": "PCSK6 Is a Key Protease in the Control of Smooth Muscle Cell Function in Vascular Remodeling.", "authors": [{"family": "Rykaczewska", "given": "Urszula", "initials": "U"}, {"family": "Suur", "given": "Bianca E", "initials": "BE"}, {"family": "R\u00f6hl", "given": "Samuel", "initials": "S"}, {"family": "Razuvaev", "given": "Anton", "initials": "A"}, {"family": "Lengquist", "given": "Mariette", "initials": "M"}, {"family": "Sabater-Lleal", "given": "Maria", "initials": "M"}, {"family": "van der Laan", "given": "Sander W", "initials": "SW"}, {"family": "Miller", "given": "Clint L", "initials": "CL"}, {"family": "Wirka", "given": "Robert C", "initials": "RC"}, {"family": "Kronqvist", "given": "Malin", "initials": "M"}, {"family": "Gonzalez Diez", "given": "Maria", "initials": "M"}, {"family": "Vesterlund", "given": "Mattias", "initials": "M"}, {"family": "Gillgren", "given": "Peter", "initials": "P"}, {"family": "Odeberg", "given": "Jacob", "initials": "J"}, {"family": "Lindeman", "given": "Jan H", "initials": "JH"}, {"family": "Veglia", "given": "Fabrizio", "initials": "F"}, {"family": "Humphries", "given": "Steve E", "initials": "SE"}, {"family": "de Faire", "given": "Ulf", "initials": "U"}, {"family": "Baldassarre", "given": "Damiano", "initials": "D"}, {"family": "Tremoli", "given": "Elena", "initials": "E"}, {"family": "IMPROVE study group", "given": "", "initials": ""}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Hansson", "given": "G\u00f6ran K", "initials": "GK"}, {"family": "Paulsson-Berne", "given": "Gabrielle", "initials": "G"}, {"family": "Pasterkamp", "given": "Gerard", "initials": "G"}, {"family": "Quertermous", "given": "Thomas", "initials": "T"}, {"family": "Hamsten", "given": "Anders", "initials": "A"}, {"family": "Eriksson", "given": "Per", "initials": "P"}, {"family": "Hedin", "given": "Ulf", "initials": "U"}, {"family": "Matic", "given": "Ljubica", "initials": "L"}], "type": "journal article", "published": "2020-02-28", "journal": {"volume": "126", "issn": "1524-4571", "issue": "5", "title": "Circ. Res.", "pages": "571-585", "issn-l": "0009-7330"}, "abstract": "PCSKs (Proprotein convertase subtilisins/kexins) are a protease family with unknown functions in vasculature. Previously, we demonstrated PCSK6 upregulation in human atherosclerotic plaques associated with smooth muscle cells (SMCs), inflammation, extracellular matrix remodeling, and mitogens.\n\nHere, we applied a systems biology approach to gain deeper insights into the PCSK6 role in normal and diseased vessel wall.\n\nGenetic analyses revealed association of intronic PCSK6 variant rs1531817 with maximum internal carotid intima-media thickness progression in high-cardiovascular risk subjects. This variant was linked with PCSK6 mRNA expression in healthy aortas and plaques but also with overall plaque SMA+ cell content and pericyte fraction. Increased PCSK6 expression was found in several independent human cohorts comparing atherosclerotic lesions versus healthy arteries, using transcriptomic and proteomic datasets. By immunohistochemistry, PCSK6 was localized to fibrous cap SMA+ cells and neovessels in plaques. In human, rat, and mouse intimal hyperplasia, PCSK6 was expressed by proliferating SMA+ cells and upregulated after 5 days in rat carotid balloon injury model, with positive correlation to PDGFB (platelet-derived growth factor subunit B) and MMP (matrix metalloprotease) 2/MMP14. Here, PCSK6 was shown to colocalize and cointeract with MMP2/MMP14 by in situ proximity ligation assay. Microarrays of carotid arteries from Pcsk6-/- versus control mice revealed suppression of contractile SMC markers, extracellular matrix remodeling enzymes, and cytokines/receptors. Pcsk6-/- mice showed reduced intimal hyperplasia response upon carotid ligation in vivo, accompanied by decreased MMP14 activation and impaired SMC outgrowth from aortic rings ex vivo. PCSK6 silencing in human SMCs in vitro leads to downregulation of contractile markers and increase in MMP2 expression. Conversely, PCSK6 overexpression increased PDGFBB (platelet-derived growth factor BB)-induced cell proliferation and particularly migration.\n\nPCSK6 is a novel protease that induces SMC migration in response to PDGFB, mechanistically via modulation of contractile markers and MMP14 activation. This study establishes PCSK6 as a key regulator of SMC function in vascular remodeling. Visual Overview: An online visual overview is available for this article.", "doi": "10.1161/CIRCRESAHA.119.316063", "pmid": "31893970", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Global Proteomics and Proteogenomics": "Collaborative"}, "xrefs": [], "notes": [], "created": "2020-01-14T10:04:55.756Z", "modified": "2021-11-10T12:53:44.074Z"}, {"entity": "publication", "iuid": "450f8da69f4542c8a4a21da72c872a4a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/450f8da69f4542c8a4a21da72c872a4a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/450f8da69f4542c8a4a21da72c872a4a"}}, "title": "Fine-Tuning of Sox17 and Canonical Wnt Coordinates the Permeability Properties of the Blood-Brain Barrier.", "authors": [{"family": "Corada", "given": "Monica", "initials": "M"}, {"family": "Orsenigo", "given": "Fabrizio", "initials": "F"}, {"family": "Bhat", "given": "Ganesh Parameshwar", "initials": "GP"}, {"family": "Conze", "given": "Lei Liu", "initials": "LL"}, {"family": "Breviario", "given": "Ferruccio", "initials": "F"}, {"family": "Cunha", "given": "Sara Isabel", "initials": "SI"}, {"family": "Claesson-Welsh", "given": "Lena", "initials": "L"}, {"family": "Beznoussenko", "given": "Galina V", "initials": "GV"}, {"family": "Mironov", "given": "Alexander A", "initials": "AA"}, {"family": "Bacigaluppi", "given": "Marco", "initials": "M"}, {"family": "Martino", "given": "Gianvito", "initials": "G"}, {"family": "Pitulescu", "given": "Mara E", "initials": "ME"}, {"family": "Adams", "given": "Ralf H", "initials": "RH"}, {"family": "Magnusson", "given": "Peetra", "initials": "P"}, {"family": "Dejana", "given": "Elisabetta", "initials": "E"}], "type": "journal article", "published": "2019-02-15", "journal": {"volume": "124", "issn": "1524-4571", "issue": "4", "pages": "511-525", "title": "Circ. Res.", "issn-l": "0009-7330"}, "abstract": "The microvasculature of the central nervous system includes the blood-brain barrier (BBB), which regulates the permeability to nutrients and restricts the passage of toxic agents and inflammatory cells. Canonical Wnt/\u03b2-catenin signaling is responsible for the early phases of brain vascularization and BBB differentiation. However, this signal declines after birth, and other signaling pathways able to maintain barrier integrity at postnatal stage are still unknown.\n\nSox17 (SRY [sex-determining region Y]-box 17) constitutes a major downstream target of Wnt/\u03b2-catenin in endothelial cells and regulates arterial differentiation. In the present article, we asked whether Sox17 may act downstream of Wnt/\u03b2-catenin in inducing BBB differentiation and maintenance.\n\nUsing reporter mice and nuclear staining of Sox17 and \u03b2-catenin, we report that although \u03b2-catenin signaling declines after birth, Sox17 activation increases and remains high in the adult. Endothelial-specific inactivation of Sox17 leads to increase of permeability of the brain microcirculation. The severity of this effect depends on the degree of BBB maturation: it is strong in the embryo and progressively declines after birth. In search of Sox17 mechanism of action, RNA sequencing analysis of gene expression of brain endothelial cells has identified members of the Wnt/\u03b2-catenin signaling pathway as downstream targets of Sox17. Consistently, we found that Sox17 is a positive inducer of Wnt/\u03b2-catenin signaling, and it acts in concert with this pathway to induce and maintain BBB properties. In vivo, inhibition of the \u03b2-catenin destruction complex or expression of a degradation-resistant \u03b2-catenin mutant, prevent the increase in permeability and retina vascular malformations observed in the absence of Sox17.\n\nOur data highlight a novel role for Sox17 in the induction and maintenance of the BBB, and they underline the strict reciprocal tuning of this transcription factor and Wnt/\u03b2-catenin pathway. Modulation of Sox17 activity may be relevant to control BBB permeability in pathological conditions.", "doi": "10.1161/CIRCRESAHA.118.313316", "pmid": "30591003", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC6407809"}], "notes": [], "created": "2020-01-08T12:41:49.709Z", "modified": "2021-06-21T13:33:14.416Z"}, {"entity": "publication", "iuid": "eab05309fc2d4f3f90c49cb25edf1953", "links": {"self": {"href": "https://publications.scilifelab.se/publication/eab05309fc2d4f3f90c49cb25edf1953.json"}, "display": {"href": "https://publications.scilifelab.se/publication/eab05309fc2d4f3f90c49cb25edf1953"}}, "title": "Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci.", "authors": [{"family": "Jones", "given": "Gregory T", "initials": "GT"}, {"family": "Tromp", "given": "Gerard", "initials": "G"}, {"family": "Kuivaniemi", "given": "Helena", "initials": "H"}, {"family": "Gretarsdottir", "given": "Solveig", "initials": "S"}, {"family": "Baas", "given": "Annette F", "initials": "AF"}, {"family": "Giusti", "given": "Betti", "initials": "B"}, {"family": "Strauss", "given": "Ewa", "initials": "E"}, {"family": "Van't Hof", "given": "Femke N G", "initials": "FN"}, {"family": "Webb", "given": "Thomas R", "initials": "TR"}, {"family": "Erdman", "given": "Robert", "initials": "R"}, {"family": "Ritchie", "given": "Marylyn D", "initials": "MD"}, {"family": "Elmore", "given": "James R", "initials": "JR"}, {"family": "Verma", "given": "Anurag", "initials": "A"}, {"family": "Pendergrass", "given": "Sarah", "initials": "S"}, {"family": "Kullo", "given": "Iftikhar J", "initials": "IJ"}, {"family": "Ye", "given": "Zi", "initials": "Z"}, {"family": "Peissig", "given": "Peggy L", "initials": "PL"}, {"family": "Gottesman", "given": "Omri", "initials": "O"}, {"family": "Verma", "given": "Shefali S", "initials": "SS"}, {"family": "Malinowski", "given": "Jennifer", "initials": "J"}, {"family": "Rasmussen-Torvik", "given": "Laura J", "initials": "LJ"}, {"family": "Borthwick", "given": "Kenneth M", "initials": "KM"}, {"family": "Smelser", "given": "Diane T", "initials": "DT"}, {"family": "Crosslin", "given": "David R", "initials": "DR"}, {"family": "de Andrade", "given": "Mariza", "initials": "M"}, {"family": "Ryer", "given": "Evan J", "initials": "EJ"}, {"family": "McCarty", "given": "Catherine A", "initials": "CA"}, {"family": "B\u00f6ttinger", "given": "Erwin P", "initials": "EP"}, {"family": "Pacheco", "given": "Jennifer A", "initials": "JA"}, {"family": "Crawford", "given": "Dana C", "initials": "DC"}, {"family": "Carrell", "given": "David S", "initials": "DS"}, {"family": "Gerhard", "given": "Glenn S", "initials": "GS"}, {"family": "Franklin", "given": "David P", "initials": "DP"}, {"family": "Carey", "given": "David J", "initials": "DJ"}, {"family": "Phillips", "given": "Victoria L", "initials": "VL"}, {"family": "Williams", "given": "Michael J A", "initials": "MJ"}, {"family": "Wei", "given": "Wenhua", "initials": "W"}, {"family": "Blair", "given": "Ross", "initials": "R"}, {"family": "Hill", "given": "Andrew A", "initials": "AA"}, {"family": "Vasudevan", "given": "Thodor M", "initials": "TM"}, {"family": "Lewis", "given": "David R", "initials": "DR"}, {"family": "Thomson", "given": "Ian A", "initials": "IA"}, {"family": "Krysa", "given": "Jo", "initials": "J"}, {"family": "Hill", "given": "Geraldine B", "initials": "GB"}, {"family": "Roake", "given": "Justin", "initials": "J"}, {"family": "Merriman", "given": "Tony R", "initials": "TR"}, {"family": "Oszkinis", "given": "Grzegorz", "initials": "G"}, {"family": "Galora", "given": "Silvia", "initials": "S"}, {"family": "Saracini", "given": "Claudia", "initials": "C"}, {"family": "Abbate", "given": "Rosanna", "initials": "R"}, {"family": "Pulli", "given": "Raffaele", "initials": "R"}, {"family": "Pratesi", "given": "Carlo", "initials": "C"}, {"family": "Saratzis", "given": "Athanasios", "initials": "A"}, {"family": "Verissimo", "given": "Ana R", "initials": "AR"}, {"family": "Bumpstead", "given": "Suzannah", "initials": "S"}, {"family": "Badger", "given": "Stephen A", "initials": "SA"}, {"family": "Clough", "given": "Rachel E", "initials": "RE"}, {"family": "Cockerill", "given": "Gillian", "initials": "G"}, {"family": "Hafez", "given": "Hany", "initials": "H"}, {"family": "Scott", "given": "D Julian A", "initials": "DJ"}, {"family": "Futers", "given": "T Simon", "initials": "TS"}, {"family": "Romaine", "given": "Simon P R", "initials": "SP"}, {"family": "Bridge", "given": "Katherine", "initials": "K"}, {"family": "Griffin", "given": "Kathryn J", "initials": "KJ"}, {"family": "Bailey", "given": "Marc A", "initials": "MA"}, {"family": "Smith", "given": "Alberto", "initials": "A"}, {"family": "Thompson", "given": "Matthew M", "initials": "MM"}, {"family": "van Bockxmeer", "given": "Frank M", "initials": "FM"}, {"family": "Matthiasson", "given": "Stefan E", "initials": "SE"}, {"family": "Thorleifsson", "given": "Gudmar", "initials": "G"}, {"family": "Thorsteinsdottir", "given": "Unnur", "initials": "U"}, {"family": "Blankensteijn", "given": "Jan D", "initials": "JD"}, {"family": "Teijink", "given": "Joep A W", "initials": "JA"}, {"family": "Wijmenga", "given": "Cisca", "initials": "C"}, {"family": "de Graaf", "given": "Jacqueline", "initials": "J"}, {"family": "Kiemeney", "given": "Lambertus A", "initials": "LA"}, {"family": "Lindholt", "given": "Jes S", "initials": "JS"}, {"family": "Hughes", "given": "Anne", "initials": "A"}, {"family": "Bradley", "given": "Declan T", "initials": "DT"}, {"family": "Stirrups", "given": "Kathleen", "initials": "K"}, {"family": "Golledge", "given": "Jonathan", "initials": "J"}, {"family": "Norman", "given": "Paul E", "initials": "PE"}, {"family": "Powell", "given": "Janet T", "initials": "JT"}, {"family": "Humphries", "given": "Steve E", "initials": "SE"}, {"family": "Hamby", "given": "Stephen E", "initials": "SE"}, {"family": "Goodall", "given": "Alison H", "initials": "AH"}, {"family": "Nelson", "given": "Christopher P", "initials": "CP"}, {"family": "Sakalihasan", "given": "Natzi", "initials": "N"}, {"family": "Courtois", "given": "Audrey", "initials": "A"}, {"family": "Ferrell", "given": "Robert E", "initials": "RE"}, {"family": "Eriksson", "given": "Per", "initials": "P"}, {"family": "Folkersen", "given": "Lasse", "initials": "L"}, {"family": "Franco-Cereceda", "given": "Anders", "initials": "A"}, {"family": "Eicher", "given": "John D", "initials": "JD"}, {"family": "Johnson", "given": "Andrew D", "initials": "AD"}, {"family": "Betsholtz", "given": "Christer", "initials": "C"}, {"family": "Ruusalepp", "given": "Arno", "initials": "A"}, {"family": "Franz\u00e9n", "given": "Oscar", "initials": "O"}, {"family": "Schadt", "given": "Eric E", "initials": "EE"}, {"family": "Bj\u00f6rkegren", "given": "Johan L M", "initials": "JL"}, {"family": "Lipovich", "given": "Leonard", "initials": "L"}, {"family": "Drolet", "given": "Anne M", "initials": "AM"}, {"family": "Verhoeven", "given": "Eric L", "initials": "EL"}, {"family": "Zeebregts", "given": "Clark J", "initials": "CJ"}, {"family": "Geelkerken", "given": "Robert H", "initials": "RH"}, {"family": "van Sambeek", "given": "Marc R", "initials": "MR"}, {"family": "van Sterkenburg", "given": "Steven M", "initials": "SM"}, {"family": "de Vries", "given": "Jean-Paul", "initials": "JP"}, {"family": "Stefansson", "given": "Kari", "initials": "K"}, {"family": "Thompson", "given": "John R", "initials": "JR"}, {"family": "de Bakker", "given": "Paul I W", "initials": "PI"}, {"family": "Deloukas", "given": "Panos", "initials": "P"}, {"family": "Sayers", "given": "Robert D", "initials": "RD"}, {"family": "Harrison", "given": "Seamus C", "initials": "SC"}, {"family": "van Rij", "given": "Andre M", "initials": "AM"}, {"family": "Samani", "given": "Nilesh J", "initials": "NJ"}, {"family": "Bown", "given": "Matthew J", "initials": "MJ"}], "type": "journal article", "published": "2017-01-20", "journal": {"volume": "120", "issn": "1524-4571", "issue": "2", "pages": "341-353", "title": "Circ. Res.", "issn-l": "0009-7330"}, "abstract": "Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA.\n\nTo identify additional AAA risk loci using data from all available genome-wide association studies.\n\nThrough a meta-analysis of 6 genome-wide association study data sets and a validation study totaling 10\u2009204 cases and 107\u2009766 controls, we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches, we observed no new associations between the lead AAA single nucleotide polymorphisms and coronary artery disease, blood pressure, lipids, or diabetes mellitus. Network analyses identified ERG, IL6R, and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9.\n\nThe 4 new risk loci for AAA seem to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease.", "doi": "10.1161/CIRCRESAHA.116.308765", "pmid": "27899403", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "CIRCRESAHA.116.308765"}, {"db": "pmc", "key": "PMC5253231"}, {"db": "mid", "key": "EMS70602"}], "notes": [], "created": "2017-05-03T13:01:54.332Z", "modified": "2024-01-16T13:48:48.666Z"}, {"entity": "publication", "iuid": "9a5dc299283048b59b8005648c9de932", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9a5dc299283048b59b8005648c9de932.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9a5dc299283048b59b8005648c9de932"}}, "title": "Identifying Novel Gene Variants in Coronary Artery Disease and Shared Genes With Several Cardiovascular Risk Factors.", "authors": [{"family": "LeBlanc", "given": "Marissa", "initials": "M"}, {"family": "Zuber", "given": "Verena", "initials": "V"}, {"family": "Andreassen", "given": "Bettina Kulle", "initials": "BK"}, {"family": "Witoelar", "given": "Aree", "initials": "A"}, {"family": "Zeng", "given": "Lingyao", "initials": "L"}, {"family": "Bettella", "given": "Francesco", "initials": "F"}, {"family": "Wang", "given": "Yunpeng", "initials": "Y"}, {"family": "McEvoy", "given": "Linda K", "initials": "LK"}, {"family": "Thompson", "given": "Wesley K", "initials": "WK"}, {"family": "Schork", "given": "Andrew J", "initials": "AJ"}, {"family": "Reppe", "given": "Sjur", "initials": "S"}, {"family": "Barrett-Connor", "given": "Elizabeth", "initials": "E"}, {"family": "Ligthart", "given": "Symen", "initials": "S"}, {"family": "Dehghan", "given": "Abbas", "initials": "A"}, {"family": "Gautvik", "given": "Kaare M", "initials": "KM"}, {"family": "Nelson", "given": "Christopher P", "initials": "CP"}, {"family": "Schunkert", "given": "Heribert", "initials": "H"}, {"family": "Samani", "given": "Nilesh J", "initials": "NJ"}, {"family": "CARDIoGRAM Consortium", "given": null, "initials": null}, {"family": "Ridker", "given": "Paul M", "initials": "PM"}, {"family": "Chasman", "given": "Daniel I", "initials": "DI"}, {"family": "Aukrust", "given": "P\u00e5l", "initials": "P"}, {"family": "Djurovic", "given": "Srdjan", "initials": "S"}, {"family": "Frigessi", "given": "Arnoldo", "initials": "A"}, {"family": "Desikan", "given": "Rahul S", "initials": "RS"}, {"family": "Dale", "given": "Anders M", "initials": "AM"}, {"family": "Andreassen", "given": "Ole A", "initials": "OA"}], "type": "journal article", "published": "2016-01-08", "journal": {"volume": "118", "issn": "1524-4571", "issue": "1", "pages": "83-94", "title": "Circ. Res.", "issn-l": "0009-7330"}, "abstract": "Coronary artery disease (CAD) is a critical determinant of morbidity and mortality. Previous studies have identified several cardiovascular disease risk factors, which may partly arise from a shared genetic basis with CAD, and thus be useful for discovery of CAD genes.\n\nWe aimed to improve discovery of CAD genes and inform the pathogenic relationship between CAD and several cardiovascular disease risk factors using a shared polygenic signal-informed statistical framework.\n\nUsing genome-wide association studies summary statistics and shared polygenic pleiotropy-informed conditional and conjunctional false discovery rate methodology, we systematically investigated genetic overlap between CAD and 8 traits related to cardiovascular disease risk factors: low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, type 2 diabetes mellitus, C-reactive protein, body mass index, systolic blood pressure, and type 1 diabetes mellitus. We found significant enrichment of single-nucleotide polymorphisms associated with CAD as a function of their association with low-density lipoprotein, high-density lipoprotein, triglycerides, type 2 diabetes mellitus, C-reactive protein, body mass index, systolic blood pressure, and type 1 diabetes mellitus. Applying the conditional false discovery rate method to the enriched phenotypes, we identified 67 novel loci associated with CAD (overall conditional false discovery rate <0.01). Furthermore, we identified 53 loci with significant effects in both CAD and at least 1 of low-density lipoprotein, high-density lipoprotein, triglycerides, type 2 diabetes mellitus, C-reactive protein, systolic blood pressure, and type 1 diabetes mellitus.\n\nThe observed polygenic overlap between CAD and cardiometabolic risk factors indicates a pathogenic relation that warrants further investigation. The new gene loci identified implicate novel genetic mechanisms related to CAD.", "doi": "10.1161/CIRCRESAHA.115.306629", "pmid": "26487741", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "CIRCRESAHA.115.306629"}], "notes": [], "created": "2017-05-03T13:01:54.027Z", "modified": "2020-01-21T13:56:03.963Z"}, {"entity": "publication", "iuid": "a19b8f04ff8a4fa8902afc4c54a0627f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a19b8f04ff8a4fa8902afc4c54a0627f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a19b8f04ff8a4fa8902afc4c54a0627f"}}, "title": "Identification of cis- and trans-acting genetic variants explaining up to half the variation in circulating vascular endothelial growth factor levels.", "authors": [{"family": "Debette", "given": "Stephanie", "initials": "S"}, {"family": "Visvikis-Siest", "given": "Sophie", "initials": "S"}, {"family": "Chen", "given": "Ming-Huen", "initials": "MH"}, {"family": "Ndiaye", "given": "Ndeye-Coumba", "initials": "NC"}, {"family": "Song", "given": "Ci", "initials": "C"}, {"family": "Destefano", "given": "Anita", "initials": "A"}, {"family": "Safa", "given": "Radwan", "initials": "R"}, {"family": "Azimi Nezhad", "given": "Mohsen", "initials": "M"}, {"family": "Sawyer", "given": "Douglas", "initials": "D"}, {"family": "Marteau", "given": "Jean-Brice", "initials": "JB"}, {"family": "Xanthakis", "given": "Vanessa", "initials": "V"}, {"family": "Siest", "given": "Gerard", "initials": "G"}, {"family": "Sullivan", "given": "Lisa", "initials": "L"}, {"family": "Pfister", "given": "Michele", "initials": "M"}, {"family": "Smith", "given": "Holly", "initials": "H"}, {"family": "Choi", "given": "Seung-Hoan", "initials": "SH"}, {"family": "Lamont", "given": "John", "initials": "J"}, {"family": "Lind", "given": "Lars", "initials": "L"}, {"family": "Yang", "given": "Qiong", "initials": "Q"}, {"family": "Fitzgerald", "given": "Peter", "initials": "P"}, {"family": "Ingelsson", "given": "Erik", "initials": "E"}, {"family": "Vasan", "given": "Ramachandran S", "initials": "RS"}, {"family": "Seshadri", "given": "Sudha", "initials": "S"}], "type": "comparative study", "published": "2011-08-19", "journal": {"volume": "109", "issn": "1524-4571", "issue": "5", "pages": "554-563", "title": "Circ. Res.", "issn-l": "0009-7330"}, "abstract": "Vascular endothelial growth factor (VEGF) affects angiogenesis, atherosclerosis, and cancer. Although the heritability of circulating VEGF levels is high, little is known about its genetic underpinnings.\n\nOur aim was to identify genetic variants associated with circulating VEGF levels, using an unbiased genome-wide approach, and to explore their functional significance with gene expression and pathway analysis.\n\nWe undertook a genome-wide association study of serum VEGF levels in 3527 participants of the Framingham Heart Study, with preplanned replication in 1727 participants from 2 independent samples, the STANISLAS Family Study and the Prospective Investigation of the Vasculature in Uppsala Seniors study. One hundred forty single nucleotide polymorphism (SNPs) reached genome-wide significance (P<5\u00d710(-8)). We found evidence of replication for the most significant associations in both replication datasets. In a conditional genome-wide association study, 4 SNPs mapping to 3 chromosomal regions were independently associated with circulating VEGF levels: rs6921438 and rs4416670 (6p21.1, P=6.11\u00d710(-506) and P=1.47\u00d710(-12)), rs6993770 (8q23.1, P=2.50\u00d710(-16)), and rs10738760 (9p24.2, P=1.96\u00d710(-34)). A genetic score including these 4 SNPs explained 48% of the heritability of serum VEGF levels. Six of the SNPs that reached genome-wide significance in the genome-wide association study were significantly associated with VEGF messenger RNA levels in peripheral blood mononuclear cells. Ingenuity pathway analyses showed found plausible biological links between VEGF and 2 novel genes in these loci (ZFPM2 and VLDLR).\n\nGenetic variants explaining up to half the heritability of serum VEGF levels were identified. These new insights provide important clues to the pathways regulating circulating VEGF levels.", "doi": "10.1161/CIRCRESAHA.111.243790", "pmid": "21757650", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (SNP&SEQ Technology Platform)": null}, "xrefs": [{"db": "pii", "key": "CIRCRESAHA.111.243790"}, {"db": "pmc", "key": "PMC3193930"}, {"db": "mid", "key": "NIHMS315529"}], "notes": [], "created": "2017-05-04T15:00:41.730Z", "modified": "2020-01-21T13:56:04.152Z"}], "created": "2017-05-09T09:12:24.109Z", "modified": "2020-11-27T13:14:04.533Z"}