{"entity": "journal", "iuid": "b3aa6589b39148d4a47149c9a0ca3ddd", "timestamp": "2026-09-12T07:37:38.043Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/journal/Circulation.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/journal/Circulation"}}, "title": "Circulation", "issn": "1524-4539", "issn-l": "0009-7322", "publications_count": 13, "publications": [{"entity": "publication", "iuid": "c804939c8e134ac29252c0780fdc327f", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/c804939c8e134ac29252c0780fdc327f.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/c804939c8e134ac29252c0780fdc327f"}}, "title": "Abstract 072: Plasma Metabolome Predicts Long-term Body Weight Gain and Type 2 Diabetes in Non-Obese Individuals", "authors": [{"family": "Wu", "given": "Zhiyuan", "initials": "Z"}, {"family": "Liu", "given": "Binkai", "initials": "B"}, {"family": "Li", "given": "Jun", "initials": "J"}, {"family": "Zeleznik", "given": "Oana", "initials": "O"}, {"family": "Eliassen", "given": "A Heather", "initials": "AH"}, {"family": "Wittenbecher", "given": "Clemens", "initials": "C"}, {"family": "Hu", "given": "Frank", "initials": "F"}, {"family": "Wang", "given": "Molin", "initials": "M"}, {"family": "Song", "given": "Mingyang", "initials": "M"}, {"family": "Hu", "given": "Yang", "initials": "Y"}, {"family": "Sun", "given": "Qi", "initials": "Q"}], "type": "journal-article", "published": "2025-03-11", "journal": {"title": "Circulation", "issn": "0009-7322", "volume": "151", "issue": "Suppl_1", "issn-l": null}, "abstract": null, "doi": "10.1161/cir.151.suppl_1.072", "pmid": null, "labels": {"Clemens Wittenbecher": null, "DDLS Fellow": null}, "xrefs": [], "notes": [], "created": "2025-12-09T13:24:36.160Z", "modified": "2025-12-09T13:25:53.297Z"}, {"entity": "publication", "iuid": "e0976a02cfbd40de8686848494f4beaf", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/e0976a02cfbd40de8686848494f4beaf.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/e0976a02cfbd40de8686848494f4beaf"}}, "title": "Clonal Hematopoiesis of Indeterminate Potential With Loss of Tet2 Enhances Risk for Atrial Fibrillation Through Nlrp3 Inflammasome Activation.", "authors": [{"family": "Lin", "given": "Amy Erica", "initials": "AE", "orcid": "0000-0002-0554-2832", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ca94bff0b2bf49fda6fd77a16e6ef0fd.json"}}, {"family": "Bapat", "given": "Aneesh C", "initials": "AC", "orcid": "0000-0002-1996-522X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/aa87f4a8e0664c7e93b91941a770aa0c.json"}}, {"family": "Xiao", "given": "Ling", "initials": "L", "orcid": "0000-0002-5463-5576", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/37f99769b7f44a9d82116459fe8aea8c.json"}}, {"family": "Niroula", "given": "Abhishek", "initials": "A", "orcid": "0000-0002-5904-0635", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/05df7afc7a494ba5af8a378e5ffa53f0.json"}}, {"family": "Ye", "given": "Jiangchuan", "initials": "J"}, {"family": "Wong", "given": "Waihay J", "initials": "WJ", "orcid": "0000-0003-2023-6590", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3a4e1a5be5c54646ab5881bc338bf6cd.json"}}, {"family": "Agrawal", "given": "Mridul", "initials": "M"}, {"family": "Farady", "given": "Christopher J", "initials": "CJ", "orcid": "0000-0002-3607-9721", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3d5167b1ad30407ba72740764e1fbb83.json"}}, {"family": "Boettcher", "given": "Andreas", "initials": "A", "orcid": "0000-0002-6548-1015", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8bf2e6da2b5844e8b8e69e27905144f1.json"}}, {"family": "Hergott", "given": "Christopher B", "initials": "CB"}, {"family": "McConkey", "given": "Marie", "initials": "M", "orcid": "0000-0002-9500-018X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e5174577207f4e46b75a2f0170e76ff3.json"}}, {"family": "Flores-Bringas", "given": "Patricio", "initials": "P"}, {"family": "Shkolnik", "given": "Veronica", "initials": "V", "orcid": "0000-0002-9043-1503", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/509e4c48124649a29675f21de034504f.json"}}, {"family": "Bick", "given": "Alexander G", "initials": "AG", "orcid": "0000-0001-5824-9595", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d2da5a35a4984921b19dfafe64cea2de.json"}}, {"family": "Milan", "given": "David", "initials": "D", "orcid": "0000-0003-0149-3110", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0f5f95aea4ec44da99d8b4bfa2fe9ba2.json"}}, {"family": "Natarajan", "given": "Pradeep", "initials": "P", "orcid": "0000-0001-8402-7435", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fe8bd48c61c047cd8e61c35d9e9ac650.json"}}, {"family": "Libby", "given": "Peter", "initials": "P", "orcid": "0000-0002-1502-502X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/39fb20acff0442bd92fc7931d3ee6cf9.json"}}, {"family": "Ellinor", "given": "Patrick T", "initials": "PT", "orcid": "0000-0002-2067-0533", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fd1830794e884e6e849fd4f7645c9b61.json"}}, {"family": "Ebert", "given": "Benjamin L", "initials": "BL", "orcid": "0000-0003-0197-5451", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/56e4f1c53a4348e2b0ceb44a38850a17.json"}}], "type": "journal article", "published": "2024-04-30", "journal": {"title": "Circulation", "issn": "1524-4539", "volume": "149", "issue": "18", "pages": "1419-1434", "issn-l": "0009-7322"}, "abstract": "Clonal hematopoiesis of indeterminate potential (CHIP), a common age-associated phenomenon, associates with increased risk of both hematological malignancy and cardiovascular disease. Although CHIP is known to increase the risk of myocardial infarction and heart failure, the influence of CHIP in cardiac arrhythmias, such as atrial fibrillation (AF), is less explored.\n\nCHIP prevalence was determined in the UK Biobank, and incident AF analysis was stratified by CHIP status and clone size using Cox proportional hazard models. Lethally irradiated mice were transplanted with hematopoietic-specific loss of Tet2, hematopoietic-specific loss of Tet2 and Nlrp3, or wild-type control and fed a Western diet, compounded with or without NLRP3 (NLR [NACHT, LRR {leucine rich repeat}] family pyrin domain containing protein 3) inhibitor, NP3-361, for 6 to 9 weeks. Mice underwent in vivo invasive electrophysiology studies and ex vivo optical mapping. Cardiomyocytes from Ldlr-/- mice with hematopoietic-specific loss of Tet2 or wild-type control and fed a Western diet were isolated to evaluate calcium signaling dynamics and analysis. Cocultures of pluripotent stem cell-derived atrial cardiomyocytes were incubated with Tet2-deficient bone marrow-derived macrophages, wild-type control, or cytokines IL-1\u03b2 (interleukin 1\u03b2) or IL-6 (interleukin 6).\n\nAnalysis of the UK Biobank showed individuals with CHIP, in particular TET2 CHIP, have increased incident AF. Hematopoietic-specific inactivation of Tet2 increases AF propensity in atherogenic and nonatherogenic mouse models and is associated with increased Nlrp3 expression and CaMKII (Ca2+/calmodulin-dependent protein kinase II) activation, with AF susceptibility prevented by inactivation of Nlrp3. Cardiomyocytes isolated from Ldlr-/- mice with hematopoietic inactivation of Tet2 and fed a Western diet have impaired calcium release from the sarcoplasmic reticulum into the cytosol, contributing to atrial arrhythmogenesis. Abnormal sarcoplasmic reticulum calcium release was recapitulated in cocultures of cardiomyocytes with the addition of Tet2-deficient macrophages or cytokines IL-1\u03b2 or IL-6.\n\nWe identified a modest association between CHIP, particularly TET2 CHIP, and incident AF in the UK Biobank population. In a mouse model of AF resulting from hematopoietic-specific inactivation of Tet2, we propose altered calcium handling as an arrhythmogenic mechanism, dependent on Nlrp3 inflammasome activation. Our data are in keeping with previous studies of CHIP in cardiovascular disease, and further studies into the therapeutic potential of NLRP3 inhibition for individuals with TET2 CHIP may be warranted.", "doi": "10.1161/CIRCULATIONAHA.123.065597", "pmid": "38357791", "labels": {"Abhishek Niroula": null, "DDLS Fellow": null}, "xrefs": [{"db": "mid", "key": "NIHMS1962305"}, {"db": "pmc", "key": "PMC11058018"}], "notes": [], "created": "2025-03-18T15:48:47.159Z", "modified": "2025-03-18T15:49:10.531Z"}, {"entity": "publication", "iuid": "67d2ee8de9e243d6b5566686c797a116", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/67d2ee8de9e243d6b5566686c797a116.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/67d2ee8de9e243d6b5566686c797a116"}}, "title": "Response by Sayols-Baixeras et al to Letter Regarding Article, \"Streptococcus Species Abundance in the Gut Is Linked to Subclinical Coronary Atherosclerosis in 8973 Participants From the SCAPIS Cohort\".", "authors": [{"family": "Sayols-Baixeras", "given": "Sergi", "initials": "S", "orcid": "0000-0002-1181-6262", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/13c5c3ffbe8f4ffda8cabbf2d0664906.json"}}, {"family": "Dekkers", "given": "Koen F", "initials": "KF"}, {"family": "Orho-Melander", "given": "Marju", "initials": "M", "orcid": "0000-0002-3578-2503", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/09f3f572ea914566930761d3dcf189b0.json"}}, {"family": "Fall", "given": "Tove", "initials": "T", "orcid": "0000-0003-2071-5866", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7dbbd468e6da4727b69333ade942c071.json"}}], "type": "letter", "published": "2024-01-16", "journal": {"title": "Circulation", "issn": "1524-4539", "volume": "149", "issue": "3", "pages": "276", "issn-l": "0009-7322"}, "abstract": null, "doi": "10.1161/CIRCULATIONAHA.123.067678", "pmid": "38227717", "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T12:16:09.129Z", "modified": "2026-08-21T09:32:53.875Z"}, {"entity": "publication", "iuid": "8af06b272b154fac9f50b3bc455e6b3e", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/8af06b272b154fac9f50b3bc455e6b3e.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/8af06b272b154fac9f50b3bc455e6b3e"}}, "title": "Streptococcus Species Abundance in the Gut Is Linked to Subclinical Coronary Atherosclerosis in 8973 Participants From the SCAPIS Cohort.", "authors": [{"family": "Sayols-Baixeras", "given": "Sergi", "initials": "S", "orcid": "0000-0002-1181-6262", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/13c5c3ffbe8f4ffda8cabbf2d0664906.json"}}, {"family": "Dekkers", "given": "Koen F", "initials": "KF"}, {"family": "Baldanzi", "given": "Gabriel", "initials": "G"}, {"family": "J\u00f6nsson", "given": "Daniel", "initials": "D", "orcid": "0000-0001-8298-539X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a6a28f0ea6264c3893bbd362355ec85c.json"}}, {"family": "Hammar", "given": "Ulf", "initials": "U"}, {"family": "Lin", "given": "Yi-Ting", "initials": "YT"}, {"family": "Ahmad", "given": "Shafqat", "initials": "S", "orcid": "0000-0002-3873-7943", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/13bd5f11f5cc4420a1c57183bb8323c9.json"}}, {"family": "Nguyen", "given": "Diem", "initials": "D", "orcid": "0000-0002-9680-5772", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5b12f13041f343e19fd4566678181b69.json"}}, {"family": "Varotsis", "given": "Georgios", "initials": "G", "orcid": "0000-0002-3320-2448", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9a30a9d8a223487a955992023a18658e.json"}}, {"family": "Pita", "given": "Sara", "initials": "S", "orcid": "0000-0002-5163-7306", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/dc61e356bdb84493813be139de58922a.json"}}, {"family": "Nielsen", "given": "Nynne", "initials": "N"}, {"family": "Eklund", "given": "Aron C", "initials": "AC", "orcid": "0000-0003-0861-1001", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ee40b4fbb47f4d80ab454cdc064e1ea3.json"}}, {"family": "Holm", "given": "Jacob B", "initials": "JB", "orcid": "0000-0003-1756-0875", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/27bea3fb86174b0da08cbaf68820ae98.json"}}, {"family": "Nielsen", "given": "H Bj\u00f8rn", "initials": "HB", "orcid": "0000-0003-2281-5713", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f42a7caf34014b1186783a3662375dd0.json"}}, {"family": "Ericson", "given": "Ulrika", "initials": "U"}, {"family": "Brunkwall", "given": "Louise", "initials": "L"}, {"family": "Ottosson", "given": "Filip", "initials": "F"}, {"family": "Larsson", "given": "Anna", "initials": "A"}, {"family": "Ericson", "given": "Dan", "initials": "D", "orcid": "0000-0003-0356-2351", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a89ea38f5bb6487abe6f6973a3886019.json"}}, {"family": "Klinge", "given": "Bj\u00f6rn", "initials": "B"}, {"family": "Nilsson", "given": "Peter M", "initials": "PM", "orcid": "0000-0002-5652-8459", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c1fa67d262984bccbb6b45e913a09393.json"}}, {"family": "Malinovschi", "given": "Andrei", "initials": "A", "orcid": "0000-0002-4098-7765", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/394a2f4dcf5847ce98e1c758f5c4d710.json"}}, {"family": "Lind", "given": "Lars", "initials": "L", "orcid": "0000-0003-2335-8542", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bb72ba22274c49dfb8a1cc5f607b1cdf.json"}}, {"family": "Bergstr\u00f6m", "given": "G\u00f6ran", "initials": "G", "orcid": "0000-0003-4289-5722", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d414b3352a4540a68227ca7eec73cfa6.json"}}, {"family": "Sundstr\u00f6m", "given": "Johan", "initials": "J", "orcid": "0000-0003-2247-8454", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2e1b8ae02d2949acaa8c2e18349b33a1.json"}}, {"family": "\u00c4rnl\u00f6v", "given": "Johan", "initials": "J", "orcid": "0000-0002-6933-4637", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/292b3ce479bf480487f49dc793084f22.json"}}, {"family": "Engstr\u00f6m", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-8618-9152", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5faed1571d4742588095acc83e631dfc.json"}}, {"family": "Smith", "given": "J Gustav", "initials": "JG", "orcid": "0000-0001-6285-9935", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/98819c1b9e814b4388cfadc32b1f4e73.json"}}, {"family": "Orho-Melander", "given": "Marju", "initials": "M", "orcid": "0000-0002-3578-2503", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/09f3f572ea914566930761d3dcf189b0.json"}}, {"family": "Fall", "given": "Tove", "initials": "T", "orcid": "0000-0003-2071-5866", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7dbbd468e6da4727b69333ade942c071.json"}}], "type": "journal article", "published": "2023-08-08", "journal": {"title": "Circulation", "issn": "1524-4539", "volume": "148", "issue": "6", "pages": "459-472", "issn-l": "0009-7322"}, "abstract": "Gut microbiota have been implicated in atherosclerotic disease, but their relation with subclinical coronary atherosclerosis is unclear. This study aimed to identify associations between the gut microbiome and computed tomography-based measures of coronary atherosclerosis and to explore relevant clinical correlates.\n\nWe conducted a cross-sectional study of 8973 participants (50 to 65 years of age) without overt atherosclerotic disease from the population-based SCAPIS (Swedish Cardiopulmonary Bioimage Study). Coronary atherosclerosis was measured using coronary artery calcium score and coronary computed tomography angiography. Gut microbiota species abundance and functional potential were assessed with shotgun metagenomics sequencing of fecal samples, and associations with coronary atherosclerosis were evaluated with multivariable regression models adjusted for cardiovascular risk factors. Associated species were evaluated for association with inflammatory markers, metabolites, and corresponding species in saliva.\n\nThe mean age of the study sample was 57.4 years, and 53.7% were female. Coronary artery calcification was detected in 40.3%, and 5.4% had at least 1 stenosis with >50% occlusion. Sixty-four species were associated with coronary artery calcium score independent of cardiovascular risk factors, with the strongest associations observed for Streptococcus anginosus and Streptococcus oralis subsp oralis (P<1\u00d710-5). Associations were largely similar across coronary computed tomography angiography-based measurements. Out of the 64 species, 19 species, including streptococci and other species commonly found in the oral cavity, were associated with high-sensitivity C-reactive protein plasma concentrations, and 16 with neutrophil counts. Gut microbial species that are commonly found in the oral cavity were negatively associated with plasma indole propionate and positively associated with plasma secondary bile acids and imidazole propionate. Five species, including 3 streptococci, correlated with the same species in saliva and were associated with worse dental health in the Malm\u00f6 Offspring Dental Study. Microbial functional potential of dissimilatory nitrate reduction, anaerobic fatty acid \u03b2-oxidation, and amino acid degradation were associated with coronary artery calcium score.\n\nThis study provides evidence of an association of a gut microbiota composition characterized by increased abundance of Streptococcus spp and other species commonly found in the oral cavity with coronary atherosclerosis and systemic inflammation markers. Further longitudinal and experimental studies are warranted to explore the potential implications of a bacterial component in atherogenesis.", "doi": "10.1161/CIRCULATIONAHA.123.063914", "pmid": "37435755", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC10399955"}], "notes": [], "created": "2026-08-20T12:16:07.214Z", "modified": "2026-08-21T09:32:51.728Z"}, {"entity": "publication", "iuid": "4cc13510b72040c8bb9cde89ff668173", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/4cc13510b72040c8bb9cde89ff668173.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/4cc13510b72040c8bb9cde89ff668173"}}, "title": "Deep Lipidomics in Human Plasma: Cardiometabolic Disease Risk and Effect of Dietary Fat Modulation.", "authors": [{"family": "Eichelmann", "given": "Fabian", "initials": "F", "orcid": "0000-0002-3975-5596", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4f6083a259c6440ab3201d53f44a0d55.json"}}, {"family": "Sellem", "given": "Laury", "initials": "L", "orcid": "0000-0002-2697-997X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b57881c0e91f4c8d89f516f9eb6fc734.json"}}, {"family": "Wittenbecher", "given": "Clemens", "initials": "C", "orcid": "0000-0001-7792-877X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2f7d2c289b3c47d5a79d23bd48a3225a.json"}}, {"family": "J\u00e4ger", "given": "Susanne", "initials": "S", "orcid": "0000-0001-6619-0861", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/28dce9f2224f4278bd7cd44639793f8d.json"}}, {"family": "Kuxhaus", "given": "Olga", "initials": "O"}, {"family": "Prada", "given": "Marcela", "initials": "M", "orcid": "0000-0002-1159-417X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/61b493b46a934273a4bfaaaa81106987.json"}}, {"family": "Cuadrat", "given": "Rafael", "initials": "R"}, {"family": "Jackson", "given": "Kim G", "initials": "KG"}, {"family": "Lovegrove", "given": "Julie A", "initials": "JA", "orcid": "0000-0001-7633-9455", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6a3da45ee27d40349f54306b4cb77b09.json"}}, {"family": "Schulze", "given": "Matthias B", "initials": "MB", "orcid": "0000-0002-0830-5277", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/853ded2c43b64f26a8b47da7ea7b79c0.json"}}], "type": "journal article", "published": "2022-07-05", "journal": {"title": "Circulation", "issn": "1524-4539", "volume": "146", "issue": "1", "pages": "21-35", "issn-l": "0009-7322"}, "abstract": "In blood and tissues, dietary and endogenously generated fatty acids (FAs) occur in free form or as part of complex lipid molecules that collectively represent the lipidome of the respective tissue. We assessed associations of plasma lipids derived from high-resolution lipidomics with incident cardiometabolic diseases and subsequently tested if the identified risk-associated lipids were sensitive to dietary fat modification.\n\nThe EPIC Potsdam cohort study (European Prospective Investigation into Cancer and Nutrition) comprises 27 548 participants recruited within an age range of 35 to 65 years from the general population around Potsdam, Germany. We generated 2 disease-specific case cohorts on the basis of a fixed random subsample (n=1262) and all respective cohort-wide identified incident primary cardiovascular disease (composite of fatal and nonfatal myocardial infarction and stroke; n=551) and type 2 diabetes (n=775) cases. We estimated the associations of baseline plasma concentrations of 282 class-specific FA abundances (calculated from 940 distinct molecular species across 15 lipid classes) with the outcomes in multivariable-adjusted Cox models. We tested the effect of an isoenergetic dietary fat modification on risk-associated lipids in the DIVAS randomized controlled trial (Dietary Intervention and Vascular Function; n=113). Participants consumed either a diet rich in saturated FAs (control), monounsaturated FAs, or a mixture of monounsaturated and n-6 polyunsaturated FAs for 16 weeks.\n\nSixty-nine lipids associated (false discovery rate<0.05) with at least 1 outcome (both, 8; only cardiovascular disease, 49; only type 2 diabetes, 12). In brief, several monoacylglycerols and FA16:0 and FA18:0 in diacylglycerols were associated with both outcomes; cholesteryl esters, free fatty acids, and sphingolipids were largely cardiovascular disease specific; and several (glycero)phospholipids were type 2 diabetes specific. In addition, 19 risk-associated lipids were affected (false discovery rate<0.05) by the diets rich in unsaturated dietary FAs compared with the saturated fat diet (17 in a direction consistent with a potential beneficial effect on long-term cardiometabolic risk). For example, the monounsaturated FA-rich diet decreased diacylglycerol(FA16:0) by 0.4 (95% CI, 0.5-0.3) SD units and increased triacylglycerol(FA22:1) by 0.5 (95% CI, 0.4-0.7) SD units.\n\nWe identified several lipids associated with cardiometabolic disease risk. A subset was beneficially altered by a dietary fat intervention that supports the substitution of dietary saturated FAs with unsaturated FAs as a potential tool for primary disease prevention.", "doi": "10.1161/CIRCULATIONAHA.121.056805", "pmid": "35422138", "labels": {"Clemens Wittenbecher": null, "DDLS Fellow": null}, "xrefs": [{"db": "pmc", "key": "PMC9241667"}], "notes": [], "created": "2025-12-09T13:38:54.335Z", "modified": "2025-12-09T13:38:54.506Z"}, {"entity": "publication", "iuid": "fe20a85245624d24a5969df04b3a7ae4", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/fe20a85245624d24a5969df04b3a7ae4.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/fe20a85245624d24a5969df04b3a7ae4"}}, "title": "Abstract 016: Artificially Sweetened Beverage Consumption, Plasma Metabolomics, And Risk Of Type 2 Diabetes Among US Adults", "authors": [{"family": "Haslam", "given": "Danielle E", "initials": "DE"}, {"family": "Wang", "given": "Biqi", "initials": "B"}, {"family": "Li", "given": "Jun", "initials": "J"}, {"family": "Guasch", "given": "Marta", "initials": "M"}, {"family": "Liang", "given": "Liming", "initials": "L"}, {"family": "Clish", "given": "Clary B", "initials": "CB"}, {"family": "Manson", "given": "Joann E", "initials": "JE"}, {"family": "Tobias", "given": "Deirdre K", "initials": "DK"}, {"family": "Wittenbecher", "given": "Clemens", "initials": "C"}, {"family": "Willett", "given": "Walter C", "initials": "WC"}, {"family": "Stampfer", "given": "Meir J", "initials": "MJ"}, {"family": "Herman", "given": "Mark A", "initials": "MA"}, {"family": "Dupuis", "given": "Josee", "initials": "J"}, {"family": "McKeown", "given": "Nicola M", "initials": "NM"}, {"family": "Malik", "given": "Vasanti S", "initials": "VS"}, {"family": "Meigs", "given": "James B", "initials": "JB"}, {"family": "Hu", "given": "Frank B", "initials": "FB"}, {"family": "Bhupathiraju", "given": "Shilpa N", "initials": "SN"}], "type": "journal-article", "published": "2022-03-00", "journal": {"title": "Circulation", "issn": "0009-7322", "volume": "145", "issue": "Suppl_1", "issn-l": null}, "abstract": null, "doi": "10.1161/circ.145.suppl_1.016", "pmid": null, "labels": {"Clemens Wittenbecher": null, "DDLS Fellow": null}, "xrefs": [], "notes": [], "created": "2025-12-09T13:38:50.249Z", "modified": "2025-12-09T13:38:50.257Z"}, {"entity": "publication", "iuid": "4cc8e73c3cc74c208b1d8b5d1cc805bd", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/4cc8e73c3cc74c208b1d8b5d1cc805bd.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/4cc8e73c3cc74c208b1d8b5d1cc805bd"}}, "title": "Premature Menopause, Clonal Hematopoiesis, and Coronary Artery Disease in Postmenopausal Women.", "authors": [{"family": "Honigberg", "given": "Michael C", "initials": "MC"}, {"family": "Zekavat", "given": "Seyedeh M", "initials": "SM"}, {"family": "Niroula", "given": "Abhishek", "initials": "A"}, {"family": "Griffin", "given": "Gabriel K", "initials": "GK"}, {"family": "Bick", "given": "Alexander G", "initials": "AG"}, {"family": "Pirruccello", "given": "James P", "initials": "JP"}, {"family": "Nakao", "given": "Tetsushi", "initials": "T"}, {"family": "Whitsel", "given": "Eric A", "initials": "EA"}, {"family": "Farland", "given": "Leslie V", "initials": "LV"}, {"family": "Laurie", "given": "Cecelia", "initials": "C"}, {"family": "Kooperberg", "given": "Charles", "initials": "C"}, {"family": "Manson", "given": "JoAnn E", "initials": "JE"}, {"family": "Gabriel", "given": "Stacey", "initials": "S"}, {"family": "Libby", "given": "Peter", "initials": "P"}, {"family": "Reiner", "given": "Alexander P", "initials": "AP"}, {"family": "Ebert", "given": "Benjamin L", "initials": "BL"}, {"family": "NHLBI Trans-Omics for Precision Medicine Program", "given": "", "initials": ""}, {"family": "Natarajan", "given": "Pradeep", "initials": "P"}], "type": "journal article", "published": "2021-02-02", "journal": {"title": "Circulation", "issn": "1524-4539", "volume": "143", "issue": "5", "pages": "410-423", "issn-l": "0009-7322"}, "abstract": "Premature menopause is an independent risk factor for cardiovascular disease in women, but mechanisms underlying this association remain unclear. Clonal hematopoiesis of indeterminate potential (CHIP), the age-related expansion of hematopoietic cells with leukemogenic mutations without detectable malignancy, is associated with accelerated atherosclerosis. Whether premature menopause is associated with CHIP is unknown.\n\nWe included postmenopausal women from the UK Biobank (n=11 495) aged 40 to 70 years with whole exome sequences and from the Women's Health Initiative (n=8111) aged 50 to 79 years with whole genome sequences. Premature menopause was defined as natural or surgical menopause occurring before age 40 years. Co-primary outcomes were the presence of any CHIP and CHIP with variant allele frequency >0.1. Logistic regression tested the association of premature menopause with CHIP, adjusted for age, race, the first 10 principal components of ancestry, smoking, diabetes, and hormone therapy use. Secondary analyses considered natural versus surgical premature menopause and gene-specific CHIP subtypes. Multivariable-adjusted Cox models tested the association between CHIP and incident coronary artery disease.\n\nThe sample included 19 606 women, including 418 (2.1%) with natural premature menopause and 887 (4.5%) with surgical premature menopause. Across cohorts, CHIP prevalence in postmenopausal women with versus without a history of premature menopause was 8.8% versus 5.5% (P<0.001), respectively. After multivariable adjustment, premature menopause was independently associated with CHIP (all CHIP: odds ratio, 1.36 [95% 1.10-1.68]; P=0.004; CHIP with variant allele frequency >0.1: odds ratio, 1.40 [95% CI, 1.10-1.79]; P=0.007). Associations were larger for natural premature menopause (all CHIP: odds ratio, 1.73 [95% CI, 1.23-2.44]; P=0.001; CHIP with variant allele frequency >0.1: odds ratio, 1.91 [95% CI, 1.30-2.80]; P<0.001) but smaller and nonsignificant for surgical premature menopause. In gene-specific analyses, only DNMT3A CHIP was significantly associated with premature menopause. Among postmenopausal middle-aged women, CHIP was independently associated with incident coronary artery disease (hazard ratio associated with all CHIP: 1.36 [95% CI, 1.07-1.73]; P=0.012; hazard ratio associated with CHIP with variant allele frequency >0.1: 1.48 [95% CI, 1.13-1.94]; P=0.005).\n\nPremature menopause, especially natural premature menopause, is independently associated with CHIP among postmenopausal women. Natural premature menopause may serve as a risk signal for predilection to develop CHIP and CHIP-associated cardiovascular disease.", "doi": "10.1161/CIRCULATIONAHA.120.051775", "pmid": "33161765", "labels": {"Abhishek Niroula": null, "DDLS Fellow": null}, "xrefs": [{"db": "mid", "key": "NIHMS1656471"}, {"db": "pmc", "key": "PMC7911856"}], "notes": [], "created": "2023-11-20T11:21:55.796Z", "modified": "2023-11-20T11:21:55.823Z"}, {"entity": "publication", "iuid": "70ee6fdadad947d7a6ee80f146f5f60e", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/70ee6fdadad947d7a6ee80f146f5f60e.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/70ee6fdadad947d7a6ee80f146f5f60e"}}, "title": "Clinical and Genetic Determinants of Varicose Veins.", "authors": [{"family": "Fukaya", "given": "Eri", "initials": "E"}, {"family": "Flores", "given": "Alyssa M", "initials": "AM"}, {"family": "Lindholm", "given": "Daniel", "initials": "D"}, {"family": "Gustafsson", "given": "Stefan", "initials": "S"}, {"family": "Zanetti", "given": "Daniela", "initials": "D"}, {"family": "Ingelsson", "given": "Erik", "initials": "E"}, {"family": "Leeper", "given": "Nicholas J", "initials": "NJ"}], "type": "journal article", "published": "2018-12-18", "journal": {"title": "Circulation", "issn": "1524-4539", "volume": "138", "issue": "25", "pages": "2869-2880", "issn-l": "0009-7322"}, "abstract": "Varicose veins are a common problem with no approved medical therapies. Although it is believed that varicose vein pathogenesis is multifactorial, there is limited understanding of the genetic and environmental factors that contribute to their formation. Large-scale studies of risk factors for varicose veins may highlight important aspects of pathophysiology and identify groups at increased risk for disease.\n\nWe applied machine learning to agnostically search for risk factors of varicose veins in 493 519 individuals in the UK Biobank. Predictors were further studied with univariable and multivariable Cox regression analyses (2441 incident events). A genome-wide association study of varicose veins was also performed among 337 536 unrelated individuals (9577 cases) of white British descent, followed by expression quantitative loci and pathway analyses. Because height emerged as a new candidate risk factor, we performed mendelian randomization analyses to assess a potential causal role for height in varicose vein development.\n\nMachine learning confirmed several known (age, sex, obesity, pregnancy, history of deep vein thrombosis) and identified several new risk factors for varicose vein disease, including height. After adjustment for traditional risk factors in Cox regression, greater height remained independently associated with varicose veins (hazard ratio for upper versus lower quartile, 1.74; 95% CI, 1.51-2.01; P<0.0001). A genome-wide association study identified 30 new genome-wide significant loci, identifying pathways involved in vascular development and skeletal/limb biology. Mendelian randomization analysis provided evidence that increased height is causally related to varicose veins (inverse-variance weighted: odds ratio, 1.26; P=2.07\u00d710-16).\n\nUsing data from nearly a half-million individuals, we present a comprehensive genetic and epidemiological study of varicose veins. We identified novel clinical and genetic risk factors that provide pathophysiological insights and could help future improvements of treatment of varicose vein disease.", "doi": "10.1161/CIRCULATIONAHA.118.035584", "pmid": "30566020", "labels": [], "xrefs": [{"db": "mid", "key": "NIHMS1504113"}, {"db": "pmc", "key": "PMC6400474"}], "notes": [], "created": "2026-08-21T12:31:16.978Z", "modified": "2026-08-21T12:31:16.993Z"}, {"entity": "publication", "iuid": "5d1b9920137942dda01eee5d8ed5afb5", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/5d1b9920137942dda01eee5d8ed5afb5.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/5d1b9920137942dda01eee5d8ed5afb5"}}, "title": "H19 Induces Abdominal Aortic Aneurysm Development and Progression.", "authors": [{"family": "Li", "given": "Daniel Y", "initials": "DY"}, {"family": "Busch", "given": "Albert", "initials": "A"}, {"family": "Jin", "given": "Hong", "initials": "H"}, {"family": "Chernogubova", "given": "Ekaterina", "initials": "E"}, {"family": "Pelisek", "given": "Jaroslav", "initials": "J"}, {"family": "Karlsson", "given": "Joakim", "initials": "J"}, {"family": "Sennblad", "given": "Bengt", "initials": "B"}, {"family": "Liu", "given": "Shengliang", "initials": "S"}, {"family": "Lao", "given": "Shen", "initials": "S"}, {"family": "Hofmann", "given": "Patrick", "initials": "P"}, {"family": "B\u00e4cklund", "given": "Alexandra", "initials": "A"}, {"family": "Eken", "given": "Suzanne M", "initials": "SM"}, {"family": "Roy", "given": "Joy", "initials": "J"}, {"family": "Eriksson", "given": "Per", "initials": "P"}, {"family": "Dacken", "given": "Brian", "initials": "B"}, {"family": "Ramanujam", "given": "Deepak", "initials": "D"}, {"family": "Dueck", "given": "Anne", "initials": "A"}, {"family": "Engelhardt", "given": "Stefan", "initials": "S"}, {"family": "Boon", "given": "Reinier A", "initials": "RA"}, {"family": "Eckstein", "given": "Hans-Henning", "initials": "HH"}, {"family": "Spin", "given": "Joshua M", "initials": "JM"}, {"family": "Tsao", "given": "Philip S", "initials": "PS"}, {"family": "Maegdefessel", "given": "Lars", "initials": "L"}], "type": "journal article", "published": "2018-10-09", "journal": {"title": "Circulation", "issn": "1524-4539", "volume": "138", "issue": "15", "pages": "1551-1568", "issn-l": "0009-7322"}, "abstract": "Long noncoding RNAs have emerged as critical molecular regulators in various biological processes and diseases. Here we sought to identify and functionally characterize long noncoding RNAs as potential mediators in abdominal aortic aneurysm development.\n\nWe profiled RNA transcript expression in 2 murine abdominal aortic aneurysm models, Angiotensin II (ANGII) infusion in apolipoprotein E-deficient ( ApoE-/-) mice (n=8) and porcine pancreatic elastase instillation in C57BL/6 wild-type mice (n=12). The long noncoding RNA H19 was identified as 1 of the most highly upregulated transcripts in both mouse aneurysm models compared with sham-operated controls. This was confirmed by quantitative reverse transcription-polymerase chain reaction and in situ hybridization.\n\nExperimental knock-down of H19, utilizing site-specific antisense oligonucleotides (LNA-GapmeRs) in vivo, significantly limited aneurysm growth in both models. Upregulated H19 correlated with smooth muscle cell (SMC) content and SMC apoptosis in progressing aneurysms. Importantly, a similar pattern could be observed in human abdominal aortic aneurysm tissue samples, and in a novel preclinical LDLR-/- (low-density lipoprotein receptor) Yucatan mini-pig aneurysm model. In vitro knock-down of H19 markedly decreased apoptotic rates of cultured human aortic SMCs, whereas overexpression of H19 had the opposite effect. Notably, H19-dependent apoptosis mechanisms in SMCs appeared to be independent of miR-675, which is embedded in the first exon of the H19 gene. A customized transcription factor array identified hypoxia-inducible factor 1\u03b1 as the main downstream effector. Increased SMC apoptosis was associated with cytoplasmic interaction between H19 and hypoxia-inducible factor 1\u03b1 and sequential p53 stabilization. Additionally, H19 induced transcription of hypoxia-inducible factor 1\u03b1 via recruiting the transcription factor specificity protein 1 to the promoter region.\n\nThe long noncoding RNA H19 is a novel regulator of SMC survival in abdominal aortic aneurysm development and progression. Inhibition of H19 expression might serve as a novel molecular therapeutic target for aortic aneurysm disease.", "doi": "10.1161/CIRCULATIONAHA.117.032184", "pmid": "29669788", "labels": [], "xrefs": [{"db": "mid", "key": "NIHMS962053"}, {"db": "pmc", "key": "PMC6193867"}, {"db": "pii", "key": "CIRCULATIONAHA.117.032184"}], "notes": [], "created": "2026-08-21T12:31:14.866Z", "modified": "2026-08-21T12:31:14.899Z"}, {"entity": "publication", "iuid": "f4f070a77f374ce6b284a119bb77bc19", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/f4f070a77f374ce6b284a119bb77bc19.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/f4f070a77f374ce6b284a119bb77bc19"}}, "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", "volume": "138", "issue": "6", "pages": "590-599", "issn-l": "0009-7322"}, "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": [], "xrefs": [{"db": "pii", "key": "CIRCULATIONAHA.117.030414"}], "notes": [], "created": "2019-01-17T13:57:28.801Z", "modified": "2026-08-21T09:32:49.885Z"}, {"entity": "publication", "iuid": "9e2eda665730476f88e24a46b6a008ba", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/9e2eda665730476f88e24a46b6a008ba.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/9e2eda665730476f88e24a46b6a008ba"}}, "title": "Associations of Fitness, Physical Activity, Strength, and Genetic Risk With Cardiovascular Disease: Longitudinal Analyses in the UK Biobank Study.", "authors": [{"family": "Tikkanen", "given": "Emmi", "initials": "E"}, {"family": "Gustafsson", "given": "Stefan", "initials": "S"}, {"family": "Ingelsson", "given": "Erik", "initials": "E"}], "type": "journal article", "published": "2018-06-12", "journal": {"title": "Circulation", "issn": "1524-4539", "volume": "137", "issue": "24", "pages": "2583-2591", "issn-l": "0009-7322"}, "abstract": "Observational studies have shown inverse associations among fitness, physical activity, and cardiovascular disease. However, little is known about these associations in individuals with elevated genetic susceptibility for these diseases.\n\nWe estimated associations of grip strength, objective and subjective physical activity, and cardiorespiratory fitness with cardiovascular events and all-cause death in a large cohort of 502\u2009635 individuals from the UK Biobank (median follow-up, 6.1 years; interquartile range, 5.4-6.8 years). Then we further examined these associations in individuals with different genetic burden by stratifying individuals based on their genetic risk scores for coronary heart disease and atrial fibrillation. We compared disease risk among individuals in different tertiles of fitness, physical activity, and genetic risk using lowest tertiles as reference.\n\nGrip strength, physical activity, and cardiorespiratory fitness showed inverse associations with incident cardiovascular events (coronary heart disease: hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.77-0.81; HR, 0.95; 95% CI, 0.93-0.97; and HR, 0.68; 95% CI, 0.63-0.74, per SD change, respectively; atrial fibrillation: HR, 0.75; 95% CI, 0.73-0.76; HR, 0.93; 95% CI, 0.91-0.95; and HR, 0.60; 95% CI, 0.56-0.65, per SD change, respectively). Higher grip strength and cardiorespiratory fitness were associated with lower risk of incident coronary heart disease and atrial fibrillation in each genetic risk score group (\n                Ptrend <0.001 in each genetic risk category). In particular, high levels of cardiorespiratory fitness were associated with 49% lower risk for coronary heart disease (HR, 0.51; 95% CI, 0.38-0.69) and 60% lower risk for atrial fibrillation (HR, 0.40; 95%, CI 0.30-0.55) among individuals at high genetic risk for these diseases.\n\nFitness and physical activity demonstrated inverse associations with incident cardiovascular disease in the general population, as well as in individuals with elevated genetic risk for these diseases.", "doi": "10.1161/CIRCULATIONAHA.117.032432", "pmid": "29632216", "labels": {"Affiliated researcher": null}, "xrefs": [{"db": "pii", "key": "CIRCULATIONAHA.117.032432"}, {"db": "pmc", "key": "PMC5997501"}, {"db": "mid", "key": "NIHMS946504"}], "notes": [], "created": "2019-01-17T13:50:01.453Z", "modified": "2019-01-17T13:50:01.473Z"}, {"entity": "publication", "iuid": "c26631ab9e2845b79f81da9d39fc76fc", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/c26631ab9e2845b79f81da9d39fc76fc.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/c26631ab9e2845b79f81da9d39fc76fc"}}, "title": "Loss of Cardioprotective Effects at the ", "authors": [{"family": "Saleheen", "given": "Danish", "initials": "D"}, {"family": "Zhao", "given": "Wei", "initials": "W"}, {"family": "Young", "given": "Robin", "initials": "R"}, {"family": "Nelson", "given": "Christopher P", "initials": "CP"}, {"family": "Ho", "given": "WeangKee", "initials": "W"}, {"family": "Ferguson", "given": "Jane F", "initials": "JF"}, {"family": "Rasheed", "given": "Asif", "initials": "A"}, {"family": "Ou", "given": "Kristy", "initials": "K"}, {"family": "Nurnberg", "given": "Sylvia T", "initials": "ST"}, {"family": "Bauer", "given": "Robert C", "initials": "RC"}, {"family": "Goel", "given": "Anuj", "initials": "A"}, {"family": "Do", "given": "Ron", "initials": "R"}, {"family": "Stewart", "given": "Alexandre F R", "initials": "AFR"}, {"family": "Hartiala", "given": "Jaana", "initials": "J"}, {"family": "Zhang", "given": "Weihua", "initials": "W"}, {"family": "Thorleifsson", "given": "Gudmar", "initials": "G"}, {"family": "Strawbridge", "given": "Rona J", "initials": "RJ"}, {"family": "Sinisalo", "given": "Juha", "initials": "J"}, {"family": "Kanoni", "given": "Stavroula", "initials": "S"}, {"family": "Sedaghat", "given": "Sanaz", "initials": "S"}, {"family": "Marouli", "given": "Eirini", "initials": "E"}, {"family": "Kristiansson", "given": "Kati", "initials": "K"}, {"family": "Hua Zhao", "given": "Jing", "initials": "J"}, {"family": "Scott", "given": "Robert", "initials": "R"}, {"family": "Gauguier", "given": "Dominique", "initials": "D"}, {"family": "Shah", "given": "Svati H", "initials": "SH"}, {"family": "Smith", "given": "Albert Vernon", "initials": "AV"}, {"family": "van Zuydam", "given": "Natalie", "initials": "N"}, {"family": "Cox", "given": "Amanda J", "initials": "AJ"}, {"family": "Willenborg", "given": "Christina", "initials": "C"}, {"family": "Kessler", "given": "Thorsten", "initials": "T"}, {"family": "Zeng", "given": "Lingyao", "initials": "L"}, {"family": "Province", "given": "Michael A", "initials": "MA"}, {"family": "Ganna", "given": "Andrea", "initials": "A"}, {"family": "Lind", "given": "Lars", "initials": "L"}, {"family": "Pedersen", "given": "Nancy L", "initials": "NL"}, {"family": "White", "given": "Charles C", "initials": "CC"}, {"family": "Joensuu", "given": "Anni", "initials": "A"}, {"family": "Edi Kleber", "given": "Marcus", "initials": "M"}, {"family": "Hall", "given": "Alistair S", "initials": "AS"}, {"family": "M\u00e4rz", "given": "Winfried", "initials": "W"}, {"family": "Salomaa", "given": "Veikko", "initials": "V"}, {"family": "O'Donnell", "given": "Christopher", "initials": "C"}, {"family": "Ingelsson", "given": "Erik", "initials": "E"}, {"family": "Feitosa", "given": "Mary F", "initials": "MF"}, {"family": "Erdmann", "given": "Jeanette", "initials": "J"}, {"family": "Bowden", "given": "Donald W", "initials": "DW"}, {"family": "Palmer", "given": "Colin N A", "initials": "CNA"}, {"family": "Gudnason", "given": "Vilmundur", "initials": "V"}, {"family": "Faire", "given": "Ulf De", "initials": "U"}, {"family": "Zalloua", "given": "Pierre", "initials": "P"}, {"family": "Wareham", "given": "Nicholas", "initials": "N"}, {"family": "Thompson", "given": "John R", "initials": "JR"}, {"family": "Kuulasmaa", "given": "Kari", "initials": "K"}, {"family": "Dedoussis", "given": "George", "initials": "G"}, {"family": "Perola", "given": "Markus", "initials": "M"}, {"family": "Dehghan", "given": "Abbas", "initials": "A"}, {"family": "Chambers", "given": "John C", "initials": "JC"}, {"family": "Kooner", "given": "Jaspal", "initials": "J"}, {"family": "Allayee", "given": "Hooman", "initials": "H"}, {"family": "Deloukas", "given": "Panos", "initials": "P"}, {"family": "McPherson", "given": "Ruth", "initials": "R"}, {"family": "Stefansson", "given": "Kari", "initials": "K"}, {"family": "Schunkert", "given": "Heribert", "initials": "H"}, {"family": "Kathiresan", "given": "Sekar", "initials": "S"}, {"family": "Farrall", "given": "Martin", "initials": "M"}, {"family": "Marcel Frossard", "given": "Philippe", "initials": "P"}, {"family": "Rader", "given": "Daniel J", "initials": "DJ"}, {"family": "Samani", "given": "Nilesh J", "initials": "NJ"}, {"family": "Reilly", "given": "Muredach P", "initials": "MP"}], "type": "journal article", "published": "2017-06-13", "journal": {"title": "Circulation", "issn": "1524-4539", "volume": "135", "issue": "24", "pages": "2336-2353", "issn-l": "0009-7322"}, "abstract": "Common diseases such as coronary heart disease (CHD) are complex in etiology. The interaction of genetic susceptibility with lifestyle factors may play a prominent role. However, gene-lifestyle interactions for CHD have been difficult to identify. Here, we investigate interaction of smoking behavior, a potent lifestyle factor, with genotypes that have been shown to associate with CHD risk.\n\nWe analyzed data on 60\u2009919 CHD cases and 80\u2009243 controls from 29 studies for gene-smoking interactions for genetic variants at 45 loci previously reported to be associated with CHD risk. We also studied 5 loci associated with smoking behavior. Study-specific gene-smoking interaction effects were calculated and pooled using fixed-effects meta-analyses. Interaction analyses were declared to be significant at a \n\nWe identified novel gene-smoking interaction for a variant upstream of the ", "doi": "10.1161/CIRCULATIONAHA.116.022069", "pmid": "28461624", "labels": {"Affiliated researcher": null}, "xrefs": [{"db": "pii", "key": "CIRCULATIONAHA.116.022069"}, {"db": "pmc", "key": "PMC5612779"}, {"db": "mid", "key": "NIHMS870560"}], "notes": [], "created": "2018-12-05T11:25:49.208Z", "modified": "2018-12-05T11:25:49.227Z"}, {"entity": "publication", "iuid": "c49bf499d9e644b9ae54b218f14a962b", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/c49bf499d9e644b9ae54b218f14a962b.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/c49bf499d9e644b9ae54b218f14a962b"}}, "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"}, {"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": {"title": "Circulation", "issn": "1524-4539", "volume": "127", "issue": "13", "pages": "1404-1412", "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": [], "xrefs": [{"db": "pii", "key": "CIRCULATIONAHA.112.001233"}, {"db": "ClinicalTrials.gov", "key": "NCT00262600"}], "notes": [], "created": "2018-12-05T08:38:16.976Z", "modified": "2026-08-21T12:31:12.490Z"}], "created": "2018-12-05T08:38:16.990Z", "modified": "2020-11-27T13:12:54.895Z"}