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"Lakatta", "given": "Edward L M", "initials": "ELM", "orcid": "0000-0002-4772-0035", "researcher": {"href": "https://publications.scilifelab.se/researcher/bc797241e3fa45d7b9d8438568414f2a.json"}}, {"family": "Cheng", "given": "Ching-Yu", "initials": "C"}, {"family": "D\u00f6rr", "given": "Marcus", "initials": "M", "orcid": "0000-0001-7471-475X", "researcher": {"href": "https://publications.scilifelab.se/researcher/346fa1fbeb2e474b94f189d52d7cfb1c.json"}}, {"family": "Wong", "given": "Tien-Yin", "initials": "T"}, {"family": "Sabanayagam", "given": "Charumathi", "initials": "C", "orcid": "0000-0002-4042-4719", "researcher": {"href": "https://publications.scilifelab.se/researcher/a5ac2397f6b14194949f4dbb92a21eba.json"}}, {"family": "Oldehinkel", "given": "Albertine J", "initials": "AJ", "orcid": "0000-0003-3925-3913", "researcher": {"href": "https://publications.scilifelab.se/researcher/65ee5f9938f547bcbe51cbaf5fd7a9ba.json"}}, {"family": "Riese", "given": "Harriette", "initials": "H"}, {"family": "Lehtim\u00e4ki", "given": "Terho", "initials": "T", "orcid": "0000-0002-2555-4427", "researcher": {"href": "https://publications.scilifelab.se/researcher/03ed59707dae4c8fb9e63ac1f7c398e3.json"}}, {"family": "Verweij", "given": "Niek", "initials": "N"}, {"family": "van der Harst", "given": "Pim", "initials": "P"}], "type": "meta-analysis", "published": "2023-08-02", "journal": {"title": "Nat Commun", "issn": "2041-1723", "issn-l": "2041-1723", "volume": "14", "issue": "1", "pages": "4646"}, "abstract": "Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.", "doi": "10.1038/s41467-023-39521-2", "pmid": "37532724", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service", "NGI SNP genotyping": "Service", "Clinical Genomics Gothenburg": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC10397318"}, {"db": "pii", "key": "10.1038/s41467-023-39521-2"}], "notes": [], "created": "2023-08-14T06:18:27.304Z", "modified": "2023-11-30T22:39:21.180Z"}, {"entity": "publication", "iuid": "48f74c2afc0b4af8befb22016e4d7b0c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/48f74c2afc0b4af8befb22016e4d7b0c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/48f74c2afc0b4af8befb22016e4d7b0c"}}, "title": "Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability.", "authors": [{"family": "Lagou", "given": "Vasiliki", "initials": "V"}, {"family": "M\u00e4gi", "given": "Reedik", "initials": "R"}, {"family": "Hottenga", "given": "Jouke- Jan", "initials": "JJ", "orcid": "0000-0002-5668-2368", "researcher": {"href": "https://publications.scilifelab.se/researcher/75553b594b1f4255833de730f7f7d170.json"}}, {"family": "Grallert", "given": "Harald", "initials": "H"}, {"family": "Perry", "given": "John R B", "initials": "JRB"}, {"family": "Bouatia-Naji", "given": "Nabila", "initials": "N", "orcid": "0000-0001-5424-2134", "researcher": {"href": "https://publications.scilifelab.se/researcher/a4f7af2cb2b7464abddf05692a292fc3.json"}}, {"family": "Marullo", "given": "Letizia", "initials": "L"}, {"family": "Rybin", "given": "Denis", "initials": "D"}, {"family": "Jansen", "given": "Rick", "initials": "R", "orcid": "0000-0002-3333-6737", "researcher": {"href": 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"given": "Anders", "initials": "A"}, {"family": "Eriksson", "given": "Per", "initials": "P"}, {"family": "Jarvelin", "given": "Marjo-Riitta", "initials": "MR", "orcid": "0000-0002-2149-0630", "researcher": {"href": "https://publications.scilifelab.se/researcher/a7d00b649d284101b0501e2024fb651a.json"}}, {"family": "Stefansson", "given": "Kari", "initials": "K", "orcid": "0000-0003-1676-864X", "researcher": {"href": "https://publications.scilifelab.se/researcher/679465193fba4887a68e2aec34ccfd8e.json"}}, {"family": "Hamsten", "given": "Anders", "initials": "A"}, {"family": "Nicholson", "given": "George", "initials": "G"}, {"family": "Karpe", "given": "Fredrik", "initials": "F"}, {"family": "Dermitzakis", "given": "Emmanouil T", "initials": "ET", "orcid": "0000-0002-9302-6490", "researcher": {"href": "https://publications.scilifelab.se/researcher/3560d19929e94af1bb858a54e29a10cc.json"}}, {"family": "Lindgren", "given": "Cecilia M", "initials": "CM", "orcid": "0000-0002-4903-9374", "researcher": {"href": "https://publications.scilifelab.se/researcher/822d2f2a99814a7498f19976ed6381ef.json"}}, {"family": "McCarthy", "given": "Mark I", "initials": "MI"}, {"family": "Froguel", "given": "Philippe", "initials": "P", "orcid": "0000-0003-2972-0784", "researcher": {"href": "https://publications.scilifelab.se/researcher/34edc6a0f1b343bb8a2abd439c2ee77f.json"}}, {"family": "Kaakinen", "given": "Marika A", "initials": "MA", "orcid": "0000-0002-9228-0462", "researcher": {"href": "https://publications.scilifelab.se/researcher/0e9f40717fdd4ce29b148bc569134451.json"}}, {"family": "Lyssenko", "given": "Valeriya", "initials": "V"}, {"family": "Watanabe", "given": "Richard M", "initials": "RM", "orcid": "0000-0003-1015-0531", "researcher": {"href": "https://publications.scilifelab.se/researcher/a4336f8845ac40dfb77ef0ea1a97bbd6.json"}}, {"family": "Ingelsson", "given": "Erik", "initials": "E", "orcid": "0000-0003-2256-6972", "researcher": {"href": "https://publications.scilifelab.se/researcher/689bc741ea6547d18de7080c84d0193e.json"}}, {"family": "Florez", "given": "Jose C", "initials": "JC"}, {"family": "Dupuis", "given": "Jos\u00e9e", "initials": "J", "orcid": "0000-0003-2871-3603", "researcher": {"href": "https://publications.scilifelab.se/researcher/c9edfafda7364890866115f5343a9583.json"}}, {"family": "Barroso", "given": "In\u00eas", "initials": "I", "orcid": "0000-0001-5800-4520", "researcher": {"href": "https://publications.scilifelab.se/researcher/c2dc6be9aa194bdc9a161e551d5e6747.json"}}, {"family": "Morris", "given": "Andrew P", "initials": "AP"}, {"family": "Prokopenko", "given": "Inga", "initials": "I"}, {"family": "Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC)", "given": "", "initials": ""}], "type": "journal article", "published": "2021-01-05", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "12", "issue": "1", "pages": "24", "issn-l": "2041-1723"}, "abstract": "Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.", "doi": "10.1038/s41467-020-19366-9", "pmid": "33402679", "labels": {"NGI Stockholm (Genomics Applications)": "Service", "National Genomics Infrastructure": null, "NGI Stockholm (Genomics Production)": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": null}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-020-19366-9"}, {"db": "pmc", "key": "PMC7785747"}], "notes": [], "created": "2021-01-08T16:30:26.062Z", "modified": "2021-11-10T12:27:48.827Z"}, {"entity": "publication", "iuid": "06bdda0e02974b29a11b5fc22fa91b3b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/06bdda0e02974b29a11b5fc22fa91b3b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/06bdda0e02974b29a11b5fc22fa91b3b"}}, "title": "Genetic Predisposition to Coronary Artery Disease in Type 2 Diabetes Mellitus.", "authors": [{"family": "van Zuydam", "given": "Natalie R", "initials": "NR", "orcid": "0000-0002-9809-1398", "researcher": {"href": "https://publications.scilifelab.se/researcher/defa68cc40734fcdaffd7ba0aaad72b8.json"}}, {"family": "Ladenvall", "given": "Claes", "initials": "C", "orcid": "0000-0002-7501-6598", "researcher": {"href": "https://publications.scilifelab.se/researcher/4c5c362dc308476195eb55d2e588ba60.json"}}, {"family": "Voight", "given": "Benjamin F", "initials": "BF", "orcid": "0000-0002-6205-9994", "researcher": {"href": "https://publications.scilifelab.se/researcher/d3d9e9de96ee4983ba97efc14eb3d79b.json"}}, {"family": "Strawbridge", "given": "Rona J", "initials": "RJ", "orcid": "0000-0001-8506-3585", "researcher": {"href": "https://publications.scilifelab.se/researcher/8ac5060a3b37466dae002d4ad8f4d0ac.json"}}, {"family": "Fernandez-Tajes", "given": "Juan", "initials": "J", "orcid": "0000-0003-1515-2421", "researcher": {"href": "https://publications.scilifelab.se/researcher/dad51251fc8d42f793e4c991c4102667.json"}}, {"family": "Rayner", "given": "N William", "initials": "NW", "orcid": "0000-0003-0510-4792", "researcher": {"href": "https://publications.scilifelab.se/researcher/0e3c7e5bd20348629ba3fe232fc2bcd2.json"}}, {"family": "Robertson", "given": "Neil R", "initials": "NR"}, {"family": "Mahajan", "given": "Anubha", "initials": "A"}, {"family": "Vlachopoulou", "given": "Efthymia", "initials": "E"}, {"family": "Goel", "given": "Anuj", "initials": "A", "orcid": "0000-0003-2307-4021", "researcher": {"href": "https://publications.scilifelab.se/researcher/0f16d9d2e2164938a12b027326c21316.json"}}, {"family": "Kleber", "given": "Marcus E", "initials": "ME"}, {"family": "Nelson", "given": "Christopher P", "initials": "CP"}, {"family": "Kwee", "given": "Lydia Coulter", "initials": "LC", "orcid": "0000-0002-6997-8571", "researcher": {"href": "https://publications.scilifelab.se/researcher/aa16042af5d84f11927203fc564e8fcb.json"}}, {"family": "Esko", "given": "T\u00f5nu", "initials": "T", "orcid": "0000-0003-1982-6569", "researcher": {"href": "https://publications.scilifelab.se/researcher/d72619c1e29d44e8b8454902d2af8d9e.json"}}, {"family": "Mihailov", "given": "Evelin", "initials": "E"}, {"family": "M\u00e4gi", "given": "Reedik", "initials": "R", "orcid": "0000-0002-2964-6011", "researcher": {"href": "https://publications.scilifelab.se/researcher/61f337c26b414b8fa30bf0fdb77368a1.json"}}, {"family": "Milani", "given": "Lili", "initials": "L", "orcid": "0000-0002-5323-3102", "researcher": {"href": "https://publications.scilifelab.se/researcher/dec8d00c4b9d43458c5c895b164695d5.json"}}, {"family": "Fischer", "given": "Krista", "initials": "K", "orcid": "0000-0002-3521-0599", "researcher": {"href": "https://publications.scilifelab.se/researcher/bcd45c97a9c2450c9c88adbd83d36b24.json"}}, {"family": "Kanoni", "given": "Stavroula", "initials": "S", "orcid": "0000-0002-1691-9615", "researcher": {"href": "https://publications.scilifelab.se/researcher/95f9c5fce1fe44719ef772eda9a4f5e4.json"}}, {"family": "Kumar", "given": "Jitender", "initials": "J"}, {"family": "Song", "given": "Ci", "initials": "C"}, {"family": "Hartiala", "given": "Jaana A", "initials": "JA", "orcid": "0000-0003-4883-9318", "researcher": {"href": "https://publications.scilifelab.se/researcher/f39400df71774cf8ae408eccbe34d981.json"}}, {"family": "Pedersen", "given": "Nancy L", "initials": "NL", "orcid": "0000-0001-8057-3543", "researcher": {"href": "https://publications.scilifelab.se/researcher/cbee4e5f6d10460cac50f00ee92d5bdf.json"}}, {"family": "Perola", "given": "Markus", "initials": "M", "orcid": "0000-0003-4842-1667", "researcher": {"href": "https://publications.scilifelab.se/researcher/ef3cdf94ecb543f1a449a7704f8be7b2.json"}}, {"family": "Gieger", "given": "Christian", "initials": "C"}, {"family": "Peters", "given": "Annette", "initials": "A", "orcid": "0000-0001-6645-0985", "researcher": {"href": "https://publications.scilifelab.se/researcher/05465e52a0f6412e81752d2249af30de.json"}}, {"family": "Qu", "given": "Liming", "initials": "L"}, {"family": "Willems", "given": "Sara M", "initials": "SM", "orcid": "0000-0002-6803-3007", "researcher": {"href": "https://publications.scilifelab.se/researcher/307c8a9b3ab54ab586c7b000c110e76b.json"}}, {"family": "Doney", "given": "Alex S F", "initials": "ASF"}, {"family": "Morris", "given": "Andrew D", "initials": "AD"}, {"family": "Zheng", "given": "Yan", "initials": "Y", "orcid": "0000-0003-1129-3147", "researcher": {"href": "https://publications.scilifelab.se/researcher/c0baf9bc398345709fcfe2f635c6d443.json"}}, {"family": "Sesti", "given": "Giorgio", "initials": "G", "orcid": "0000-0002-1618-7688", "researcher": {"href": "https://publications.scilifelab.se/researcher/3c564dce3a584837a595ad7c9630092d.json"}}, {"family": "Hu", "given": "Frank B", "initials": "FB", "orcid": "0000-0002-8233-6274", "researcher": {"href": "https://publications.scilifelab.se/researcher/8cdf552612da400a9b3d72aaed260aa9.json"}}, {"family": "Qi", "given": "Lu", "initials": "L", "orcid": "0000-0002-8041-7791", "researcher": {"href": "https://publications.scilifelab.se/researcher/14b5a04081604f12859bb18b5e7c0f38.json"}}, {"family": "Laakso", "given": "Markku", "initials": "M", "orcid": "0000-0002-3394-7749", "researcher": {"href": "https://publications.scilifelab.se/researcher/13d8518be25141a296d7f2df5cccb4ee.json"}}, {"family": "Thorsteinsdottir", "given": "Unnur", "initials": "U"}, {"family": "Grallert", "given": "Harald", "initials": "H"}, {"family": "van Duijn", "given": "Cornelia", "initials": "C", "orcid": "0000-0002-2374-9204", "researcher": {"href": "https://publications.scilifelab.se/researcher/354ccf94e95f40da96e61c89a0a60adb.json"}}, {"family": "Reilly", "given": "Muredach P", "initials": "MP", "orcid": "0000-0002-3035-9386", "researcher": {"href": "https://publications.scilifelab.se/researcher/de249cb6c3774f04985a39ca9828b97e.json"}}, {"family": "Ingelsson", "given": "Erik", "initials": "E"}, {"family": "Deloukas", "given": "Panos", "initials": "P", "orcid": "0000-0001-9251-070X", "researcher": {"href": "https://publications.scilifelab.se/researcher/eb59dbd2f2204d41b801c41188611a9e.json"}}, {"family": "Kathiresan", "given": "Sek", "initials": "S", "orcid": "0000-0002-3711-7101", "researcher": {"href": "https://publications.scilifelab.se/researcher/58fd968293e94da49c506c743a74222e.json"}}, {"family": "Metspalu", "given": "Andres", "initials": "A", "orcid": "0000-0002-3718-796X", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd553a77a5a54258b4a4701f0e70a3f8.json"}}, {"family": "Shah", "given": "Svati H", "initials": "SH"}, {"family": "Sinisalo", "given": "Juha", "initials": "J", "orcid": "0000-0002-0169-5137", "researcher": {"href": "https://publications.scilifelab.se/researcher/6fde24cdfda24aed83d888da0d9b6811.json"}}, {"family": "Salomaa", "given": "Veikko", "initials": "V", "orcid": "0000-0001-7563-5324", "researcher": {"href": "https://publications.scilifelab.se/researcher/f2396c578c254e39b66538c3033c9ce9.json"}}, {"family": "Hamsten", "given": "Anders", "initials": "A"}, {"family": "Samani", "given": "Nilesh J", "initials": "NJ", "orcid": "0000-0002-3286-8133", "researcher": {"href": "https://publications.scilifelab.se/researcher/2227aaf274e8424f8408318f336f3bf1.json"}}, {"family": "M\u00e4rz", "given": "Winfried", "initials": "W"}, {"family": "Hazen", "given": "Stanley L", "initials": "SL", "orcid": "0000-0001-7124-6639", "researcher": {"href": "https://publications.scilifelab.se/researcher/abce9cd916c94667a73bc348ede57a01.json"}}, {"family": "Watkins", "given": "Hugh", "initials": "H", "orcid": "0000-0002-5287-9016", "researcher": {"href": "https://publications.scilifelab.se/researcher/7ea10989397546f9a027f88bd491bb8b.json"}}, {"family": "Saleheen", "given": "Danish", "initials": "D"}, {"family": "Morris", "given": "Andrew P", "initials": "AP"}, {"family": "Colhoun", "given": "Helen M", "initials": "HM", "orcid": "0000-0002-8345-3288", "researcher": {"href": "https://publications.scilifelab.se/researcher/e79cb60e3d734232b7cfad20c4f1c13e.json"}}, {"family": "Groop", "given": "Leif", "initials": "L"}, {"family": "McCarthy", "given": "Mark I", "initials": "MI", "orcid": "0000-0002-4393-0510", "researcher": {"href": "https://publications.scilifelab.se/researcher/5e44f4b1ca3a49cb8f83450ef9482e91.json"}}, {"family": "Palmer", "given": "Colin N A", "initials": "CNA", "orcid": "0000-0002-6415-6560", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a0f019dcb7a453a84480953a5514dd5.json"}}, {"family": "SUMMIT Steering Committee; CARDIOGRAMplusC4D Steering Committee*", "given": "", "initials": ""}], "type": "journal article", "published": "2020-12-00", "journal": {"title": "Circ Genom Precis Med", "issn": "2574-8300", "issn-l": "2574-8300", "volume": "13", "issue": "6", "pages": "e002769"}, "abstract": "Coronary artery disease (CAD) is accelerated in subjects with type 2 diabetes mellitus (T2D).\r\n\r\nTo test whether this reflects differential genetic influences on CAD risk in subjects with T2D, we performed a systematic assessment of genetic overlap between CAD and T2D in 66 643 subjects (27 708 with CAD and 24 259 with T2D). Variants showing apparent association with CAD in stratified analyses or evidence of interaction were evaluated in a further 117 787 subjects (16 694 with CAD and 11 537 with T2D).\r\n\r\nNone of the previously characterized CAD loci was found to have specific effects on CAD in T2D individuals, and a genome-wide interaction analysis found no new variants for CAD that could be considered T2D specific. When we considered the overall genetic correlations between CAD and its risk factors, we found no substantial differences in these relationships by T2D background.\r\n\r\nThis study found no evidence that the genetic architecture of CAD differs in those with T2D compared with those without T2D.", "doi": "10.1161/CIRCGEN.119.002769", "pmid": "33321069", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7748049"}], "notes": [], "created": "2021-01-07T17:01:51.462Z", "modified": "2021-12-07T13:47:48.005Z"}, {"entity": "publication", "iuid": "0a90b284f37043df85ba89a51ee5cc2a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0a90b284f37043df85ba89a51ee5cc2a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0a90b284f37043df85ba89a51ee5cc2a"}}, "title": "Genome-wide association study of angioedema induced by angiotensin-converting enzyme inhibitor and angiotensin receptor blocker treatment.", "authors": [{"family": "Rasmussen", "given": "Eva Rye", "initials": "ER"}, {"family": "Hallberg", "given": "P\u00e4r", "initials": "P"}, {"family": "Baranova", "given": "Ekaterina V", "initials": "EV"}, {"family": "Eriksson", "given": "Niclas", "initials": "N"}, {"family": "Karawajczyk", "given": "Malgorzata", "initials": "M"}, {"family": "Johansson", "given": "Caroline", "initials": "C"}, {"family": "Cavalli", "given": "Marco", "initials": "M"}, {"family": "Maroteau", "given": "Cyrielle", "initials": "C"}, {"family": "Veluchamy", "given": "Abirami", "initials": "A"}, {"family": "Islander", "given": "Gunilla", "initials": "G"}, {"family": "Hugosson", "given": "Svante", "initials": "S"}, {"family": "Terreehorst", "given": "Ingrid", "initials": "I"}, {"family": "Asselbergs", "given": "Folkert W", "initials": "FW", "orcid": "0000-0002-1692-8669", "researcher": {"href": "https://publications.scilifelab.se/researcher/7037429ef1304bdaabd837d242b1e6f5.json"}}, {"family": "Norling", "given": "Pia", "initials": "P"}, {"family": "Johansson", "given": "Hans-Erik", "initials": "HE"}, {"family": "Kohnke", "given": "Hugo", "initials": "H"}, {"family": "Syv\u00e4nen", "given": "Ann-Christine", "initials": "AC", "orcid": "0000-0002-9681-9146", "researcher": {"href": "https://publications.scilifelab.se/researcher/f7012e35025543379380cb90efd71243.json"}}, {"family": "Siddiqui", "given": "Moneeza K", "initials": "MK"}, {"family": "Lang", "given": "Chim C", "initials": "CC"}, {"family": "Magnusson", "given": "Patrik K E", "initials": "PKE", "orcid": "0000-0002-7315-7899", "researcher": {"href": "https://publications.scilifelab.se/researcher/b277b6387de142bbab91fad82d9eff09.json"}}, {"family": "Yue", "given": "Qun-Ying", "initials": "QY"}, {"family": "Wadelius", "given": "Claes", "initials": "C"}, {"family": "von Buchwald", "given": "Christian", "initials": "C"}, {"family": "Bygum", "given": "Anette", "initials": "A"}, {"family": "Alfirevic", "given": "Ana", "initials": "A"}, {"family": "Maitland-van der Zee", "given": "Anke H", "initials": "AH"}, {"family": "Palmer", "given": "Colin N A", "initials": "CNA", "orcid": "0000-0002-6415-6560", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a0f019dcb7a453a84480953a5514dd5.json"}}, {"family": "Wadelius", "given": "Mia", "initials": "M", "orcid": "0000-0002-6368-2622", "researcher": {"href": "https://publications.scilifelab.se/researcher/ec07b9869a1f4b77b734c5dc567dc630.json"}}], "type": "journal article", "published": "2020-12-00", "journal": {"title": "Pharmacogenomics J.", "issn": "1473-1150", "volume": "20", "issue": "6", "pages": "770-783", "issn-l": "1470-269X"}, "abstract": "Angioedema in the mouth or upper airways is a feared adverse reaction to angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) treatment, which is used for hypertension, heart failure and diabetes complications. This candidate gene and genome-wide association study aimed to identify genetic variants predisposing to angioedema induced by these drugs. The discovery cohort consisted of 173 cases and 4890 controls recruited in Sweden. In the candidate gene analysis, ETV6, BDKRB2, MME, and PRKCQ were nominally associated with angioedema (p < 0.05), but did not pass Bonferroni correction for multiple testing (p < 2.89 \u00d7 10-5). In the genome-wide analysis, intronic variants in the calcium-activated potassium channel subunit alpha-1 (KCNMA1) gene on chromosome 10 were significantly associated with angioedema (p < 5 \u00d7 10-8). Whilst the top KCNMA1 hit was not significant in the replication cohort (413 cases and 599 ACEi-exposed controls from the US and Northern Europe), a meta-analysis of the replication and discovery cohorts (in total 586 cases and 1944 ACEi-exposed controls) revealed that each variant allele increased the odds of experiencing angioedema 1.62 times (95% confidence interval 1.05-2.50, p = 0.030). Associated KCNMA1 variants are not known to be functional, but are in linkage disequilibrium with variants in transcription factor binding sites active in relevant tissues. In summary, our data suggest that common variation in KCNMA1 is associated with risk of angioedema induced by ACEi or ARB treatment. Future whole exome or genome sequencing studies will show whether rare variants in KCNMA1 or other genes contribute to the risk of ACEi- and ARB-induced angioedema.", "doi": "10.1038/s41397-020-0165-2", "pmid": "32080354", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41397-020-0165-2"}, {"db": "pmc", "key": "PMC7674154"}], "notes": [], "created": "2020-02-27T09:21:01.759Z", "modified": "2024-01-16T13:48:41.233Z"}, {"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": 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"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": "7ece5c90f5a84512a7eef65aed76aed2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7ece5c90f5a84512a7eef65aed76aed2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7ece5c90f5a84512a7eef65aed76aed2"}}, "title": "Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure.", "authors": [{"family": "Shah", "given": "Sonia", "initials": "S", "orcid": "0000-0001-5860-4526", "researcher": {"href": "https://publications.scilifelab.se/researcher/c6a8568b3cae476199b27818eeb19e4d.json"}}, {"family": "Henry", "given": "Albert", "initials": "A", "orcid": "0000-0001-7422-2288", "researcher": {"href": "https://publications.scilifelab.se/researcher/9b1557b87fc542eb8e4d7b733e5b79dc.json"}}, {"family": "Roselli", "given": "Carolina", "initials": "C", "orcid": "0000-0001-5267-6756", "researcher": {"href": "https://publications.scilifelab.se/researcher/1dd28aad250f42719d505c21ed76013b.json"}}, {"family": "Lin", "given": "Honghuang", "initials": "H", "orcid": "0000-0003-3043-3942", "researcher": {"href": "https://publications.scilifelab.se/researcher/9bc2f1e6bb1140dfa054376eac685d5e.json"}}, {"family": "Sveinbj\u00f6rnsson", "given": "Gar\u00f0ar", "initials": "G"}, {"family": "Fatemifar", "given": "Ghazaleh", "initials": "G"}, {"family": "Hedman", "given": "\u00c5sa K", "initials": "\u00c5K"}, {"family": "Wilk", "given": "Jemma B", "initials": "JB"}, {"family": "Morley", "given": "Michael P", "initials": "MP"}, {"family": "Chaffin", "given": "Mark D", "initials": "MD", "orcid": "0000-0002-1234-5562", "researcher": {"href": "https://publications.scilifelab.se/researcher/c73477de5ca0468ab051fd6eab7bad81.json"}}, {"family": "Helgadottir", "given": "Anna", "initials": "A", "orcid": "0000-0002-1806-2467", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b5de2b760674dbfba05df40af0eb38f.json"}}, {"family": "Verweij", "given": "Niek", "initials": "N", "orcid": "0000-0002-4303-7685", "researcher": {"href": "https://publications.scilifelab.se/researcher/7306319d42a640a483b937de588a17a4.json"}}, {"family": "Dehghan", "given": "Abbas", "initials": "A"}, {"family": "Almgren", "given": "Peter", "initials": "P", "orcid": "0000-0002-0473-0241", "researcher": {"href": "https://publications.scilifelab.se/researcher/8c1a61189c4846eaa1de74d1fd79c8bb.json"}}, {"family": "Andersson", "given": "Charlotte", "initials": "C"}, {"family": "Aragam", "given": "Krishna G", "initials": "KG"}, {"family": "\u00c4rnl\u00f6v", "given": "Johan", "initials": "J"}, {"family": "Backman", "given": "Joshua D", "initials": "JD"}, {"family": "Biggs", "given": "Mary L", "initials": "ML"}, {"family": "Bloom", "given": "Heather L", "initials": "HL"}, {"family": "Brandimarto", "given": "Jeffrey", "initials": "J"}, {"family": "Brown", "given": "Michael R", "initials": "MR"}, {"family": "Buckbinder", "given": "Leonard", "initials": "L"}, {"family": "Carey", "given": "David J", "initials": "DJ"}, {"family": "Chasman", "given": "Daniel I", "initials": "DI"}, {"family": "Chen", "given": "Xing", "initials": "X", "orcid": "0000-0002-7299-3238", "researcher": {"href": "https://publications.scilifelab.se/researcher/9d354d5ca83c4059b8151c8e67b99405.json"}}, {"family": "Chen", "given": "Xu", "initials": "X", "orcid": "0000-0002-7299-3238", "researcher": {"href": 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"orcid": "0000-0002-9791-0064", "researcher": {"href": "https://publications.scilifelab.se/researcher/a78c516158c844798199333ff183aaca.json"}}, {"family": "Luan", "given": "Jian'an", "initials": "J", "orcid": "0000-0003-3137-6337", "researcher": {"href": "https://publications.scilifelab.se/researcher/7f0ea409f1a2462dbb1b266db8fcc33a.json"}}, {"family": "Magnusson", "given": "Patrik", "initials": "P", "orcid": "0000-0002-7315-7899", "researcher": {"href": "https://publications.scilifelab.se/researcher/b277b6387de142bbab91fad82d9eff09.json"}}, {"family": "Mahajan", "given": "Anubha", "initials": "A", "orcid": "0000-0001-5585-3420", "researcher": {"href": "https://publications.scilifelab.se/researcher/194be8a851164e2ea4d004dd2febc9be.json"}}, {"family": "Margulies", "given": "Kenneth B", "initials": "KB"}, {"family": "M\u00e4rz", "given": "Winfried", "initials": "W"}, {"family": "Melander", "given": "Olle", "initials": "O"}, {"family": "Mordi", "given": "Ify R", "initials": "IR", "orcid": 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{"family": "Holmes", "given": "Michael V", "initials": "MV"}, {"family": "Cappola", "given": "Thomas P", "initials": "TP", "orcid": "0000-0002-9630-7204", "researcher": {"href": "https://publications.scilifelab.se/researcher/6cc50d241ad14477b91f83e012918181.json"}}, {"family": "Asselbergs", "given": "Folkert W", "initials": "FW", "orcid": "0000-0002-1692-8669", "researcher": {"href": "https://publications.scilifelab.se/researcher/7037429ef1304bdaabd837d242b1e6f5.json"}}, {"family": "Hingorani", "given": "Aroon D", "initials": "AD"}, {"family": "Kuchenbaecker", "given": "Karoline", "initials": "K", "orcid": "0000-0001-9726-603X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e142157c79648ce96b258ea78019829.json"}}, {"family": "Ellinor", "given": "Patrick T", "initials": "PT", "orcid": "0000-0002-2067-0533", "researcher": {"href": "https://publications.scilifelab.se/researcher/dd513dc49e0945bc8298f72d1244648d.json"}}, {"family": "Lang", "given": "Chim C", "initials": "CC"}, {"family": "Stefansson", "given": "Kari", "initials": "K"}, {"family": "Smith", "given": "J Gustav", "initials": "JG"}, {"family": "Vasan", "given": "Ramachandran S", "initials": "RS", "orcid": "0000-0001-7357-5970", "researcher": {"href": "https://publications.scilifelab.se/researcher/50ceef6f00ea4251a5e1e83cd379a506.json"}}, {"family": "Swerdlow", "given": "Daniel I", "initials": "DI"}, {"family": "Lumbers", "given": "R Thomas", "initials": "RT", "orcid": "0000-0002-9077-4741", "researcher": {"href": "https://publications.scilifelab.se/researcher/a53e4d6591db481f881ec6046d54535b.json"}}], "type": "journal article", "published": "2020-01-09", "journal": {"volume": "11", "issn": "2041-1723", "issue": "1", "pages": "163", "title": "Nat Commun", "issn-l": "2041-1723"}, "abstract": "Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.", "doi": "10.1038/s41467-019-13690-5", "pmid": "31919418", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC6952380"}, {"db": "pii", "key": "10.1038/s41467-019-13690-5"}], "notes": [], "created": "2020-01-14T10:04:57.921Z", "modified": "2023-06-19T13:01:57.741Z"}, {"entity": "publication", "iuid": "89c87476555544e39ef6bf6717603f84", "links": {"self": {"href": "https://publications.scilifelab.se/publication/89c87476555544e39ef6bf6717603f84.json"}, "display": {"href": "https://publications.scilifelab.se/publication/89c87476555544e39ef6bf6717603f84"}}, "title": "Associations of autozygosity with a broad range of human phenotypes.", "authors": [{"family": "Clark", "given": "David W", "initials": "DW", "orcid": "0000-0002-1025-9185", "researcher": {"href": "https://publications.scilifelab.se/researcher/a71ee9badf4f458d9b04ebf89f5f16c9.json"}}, {"family": "Okada", "given": "Yukinori", "initials": "Y", "orcid": "0000-0002-0311-8472", "researcher": {"href": "https://publications.scilifelab.se/researcher/40b13860bfef41959c29be2de853b456.json"}}, {"family": "Moore", "given": "Kristjan H S", "initials": "KHS", "orcid": "0000-0002-9579-4362", "researcher": {"href": "https://publications.scilifelab.se/researcher/38a8eaf6f23c4dd9a90cda85b0a998b5.json"}}, {"family": "Mason", "given": "Dan", "initials": "D", "orcid": "0000-0002-0026-9216", "researcher": {"href": "https://publications.scilifelab.se/researcher/3e9d969adc0849ab83d0080430bb6758.json"}}, {"family": "Pirastu", "given": "Nicola", "initials": "N", "orcid": "0000-0002-5363-3886", "researcher": {"href": "https://publications.scilifelab.se/researcher/badf4678d37546ce993bccb3880d4f12.json"}}, {"family": "Gandin", "given": "Ilaria", "initials": "I", "orcid": "0000-0003-3196-2491", "researcher": 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"https://publications.scilifelab.se/researcher/28a47f0e72074741a12430ffd7555a0a.json"}}, {"family": "Peyser", "given": "Patricia A", "initials": "PA"}, {"family": "Pirastu", "given": "Mario", "initials": "M"}, {"family": "Polderman", "given": "Tinca J C", "initials": "TJC", "orcid": "0000-0001-5564-301X", "researcher": {"href": "https://publications.scilifelab.se/researcher/80068e29fa614ba4a9bc0b070723ff75.json"}}, {"family": "Porteous", "given": "David J", "initials": "DJ", "orcid": "0000-0003-1249-6106", "researcher": {"href": "https://publications.scilifelab.se/researcher/b6e3ae11c02e4cb89e638e1e5ae0f50a.json"}}, {"family": "Posthuma", "given": "Danielle", "initials": "D"}, {"family": "Psaty", "given": "Bruce M", "initials": "BM"}, {"family": "Rioux", "given": "John D", "initials": "JD", "orcid": "0000-0001-7560-8326", "researcher": {"href": "https://publications.scilifelab.se/researcher/93bdd54d4d5d402481de2c66601100df.json"}}, {"family": "Rivadeneira", "given": "Fernando", "initials": "F", "orcid": "0000-0001-9435-9441", "researcher": {"href": "https://publications.scilifelab.se/researcher/f8894904d3cf4671a2e563169829322a.json"}}, {"family": "Rotimi", "given": "Charles", "initials": "C", "orcid": "0000-0001-5759-053X", "researcher": {"href": "https://publications.scilifelab.se/researcher/7fa2951fdebf4fddaad296d49b8f3f2b.json"}}, {"family": "Rotter", "given": "Jerome I", "initials": "JI", "orcid": "0000-0001-7191-1723", "researcher": {"href": "https://publications.scilifelab.se/researcher/7e9bdbf58ae94fc8b455bbbcbcaa50ce.json"}}, {"family": "Rudan", "given": "Igor", "initials": "I", "orcid": "0000-0001-6993-6884", "researcher": {"href": "https://publications.scilifelab.se/researcher/d50e1ca836e841f8a7a748ae93b59d75.json"}}, {"family": "Den Ruijter", "given": "Hester M", "initials": "HM"}, {"family": "Sanghera", "given": "Dharambir K", "initials": "DK"}, {"family": "Sattar", "given": "Naveed", "initials": "N", "orcid": "0000-0002-1604-2593", "researcher": {"href": "https://publications.scilifelab.se/researcher/80fbc7cdcfc444acb066449f80f87181.json"}}, {"family": "Schmidt", "given": "Reinhold", "initials": "R"}, {"family": "Schulze", "given": "Matthias B", "initials": "MB"}, {"family": "Schunkert", "given": "Heribert", "initials": "H"}, {"family": "Scott", "given": "Robert A", "initials": "RA"}, {"family": "Shuldiner", "given": "Alan R", "initials": "AR"}, {"family": "Sim", "given": "Xueling", "initials": "X", "orcid": "0000-0002-1233-7642", "researcher": {"href": "https://publications.scilifelab.se/researcher/3216a8d2a7264a1390a886fa09d5d648.json"}}, {"family": "Small", "given": "Neil", "initials": "N"}, {"family": "Smith", "given": "Jennifer A", "initials": "JA", "orcid": "0000-0002-3575-5468", "researcher": {"href": "https://publications.scilifelab.se/researcher/311c7381092b4143bcd2e4ef93250526.json"}}, {"family": "Sotoodehnia", "given": "Nona", "initials": "N"}, {"family": "Tai", "given": "E-Shyong", "initials": "ES"}, {"family": "Teumer", "given": "Alexander", "initials": "A", "orcid": "0000-0002-8309-094X", "researcher": {"href": "https://publications.scilifelab.se/researcher/dc9c2667a55b47a6a08aea764fab0946.json"}}, {"family": "Timpson", "given": "Nicholas J", "initials": "NJ", "orcid": "0000-0002-7141-9189", "researcher": {"href": "https://publications.scilifelab.se/researcher/764ab7a82db24557a5de0fad97bf53f3.json"}}, {"family": "Toniolo", "given": "Daniela", "initials": "D"}, {"family": "Tregouet", "given": "David-Alexandre", "initials": "DA"}, {"family": "Tuomi", "given": "Tiinamaija", "initials": "T", "orcid": "0000-0002-8306-6202", "researcher": {"href": "https://publications.scilifelab.se/researcher/19f5ce9936ca454c85f0af966acac5c0.json"}}, {"family": "Vollenweider", "given": "Peter", "initials": "P"}, {"family": "Wang", "given": "Carol A", "initials": "CA", "orcid": "0000-0002-4301-3974", "researcher": {"href": "https://publications.scilifelab.se/researcher/bf99a43c27034a68976e978b104a91d7.json"}}, {"family": "Weir", "given": "David R", "initials": "DR", "orcid": "0000-0002-1661-2402", "researcher": {"href": "https://publications.scilifelab.se/researcher/f90b7cfe829845fb8cbea9558a5c82a7.json"}}, {"family": "Whitfield", "given": "John B", "initials": "JB", "orcid": "0000-0002-1103-0876", "researcher": {"href": "https://publications.scilifelab.se/researcher/e0f61a914f9748ee9047301da8026bd7.json"}}, {"family": "Wijmenga", "given": "Cisca", "initials": "C"}, {"family": "Wong", "given": "Tien-Yin", "initials": "TY"}, {"family": "Wright", "given": "John", "initials": "J"}, {"family": "Yang", "given": "Jingyun", "initials": "J"}, {"family": "Yu", "given": "Lei", "initials": "L"}, {"family": "Zemel", "given": "Babette S", "initials": "BS"}, {"family": "Zonderman", "given": "Alan B", "initials": "AB"}, {"family": "Perola", "given": "Markus", "initials": "M"}, {"family": "Magnusson", "given": "Patrik K E", "initials": "PKE", "orcid": "0000-0002-7315-7899", "researcher": {"href": "https://publications.scilifelab.se/researcher/b277b6387de142bbab91fad82d9eff09.json"}}, {"family": "Uitterlinden", "given": "Andr\u00e9 G", "initials": "AG", "orcid": "0000-0002-7276-3387", "researcher": {"href": "https://publications.scilifelab.se/researcher/273577b238854023a9dffe34dabc3551.json"}}, {"family": "Kooner", "given": "Jaspal S", "initials": "JS"}, {"family": "Chasman", "given": "Daniel I", "initials": "DI"}, {"family": "Loos", "given": "Ruth J F", "initials": "RJF", "orcid": "0000-0002-8532-5087", "researcher": {"href": "https://publications.scilifelab.se/researcher/e5b6c24c302d42828806076ded81afe1.json"}}, {"family": "Franceschini", "given": "Nora", "initials": "N"}, {"family": "Franke", "given": "Lude", "initials": "L", "orcid": "0000-0002-5159-8802", "researcher": {"href": "https://publications.scilifelab.se/researcher/ee63161f78274a53b615c05555b81a10.json"}}, {"family": "Haley", "given": "Chris S", "initials": "CS", "orcid": "0000-0002-9811-0210", "researcher": {"href": "https://publications.scilifelab.se/researcher/c4fee769cfe84186abbc285881e0529c.json"}}, {"family": "Hayward", "given": "Caroline", "initials": "C", "orcid": "0000-0002-9405-9550", "researcher": {"href": "https://publications.scilifelab.se/researcher/cd49e9ad5a024c7ca2f1aa97d9e58eba.json"}}, {"family": "Walters", "given": "Robin G", "initials": "RG", "orcid": "0000-0002-9179-0321", "researcher": {"href": "https://publications.scilifelab.se/researcher/f36254611faa44b782b76da870e89bd3.json"}}, {"family": "Perry", "given": "John R B", "initials": "JRB"}, {"family": "Esko", "given": "T\u014dnu", "initials": "T"}, {"family": "Helgason", "given": "Agnar", "initials": "A"}, {"family": "Stefansson", "given": "Kari", "initials": "K"}, {"family": "Joshi", "given": "Peter K", "initials": "PK", "orcid": "0000-0002-6361-5059", "researcher": {"href": "https://publications.scilifelab.se/researcher/46050ddec8f64054b3bab46c5016aebf.json"}}, {"family": "Kubo", "given": "Michiaki", "initials": "M"}, {"family": "Wilson", "given": "James F", "initials": "JF", "orcid": "0000-0001-5751-9178", "researcher": {"href": "https://publications.scilifelab.se/researcher/b39e6e0f7210494cb4f80be0f7413b6f.json"}}], "type": "journal article", "published": "2019-10-31", "journal": {"volume": "10", "issn": "2041-1723", "issue": "1", "pages": "4957", "title": "Nat Commun", "issn-l": "2041-1723"}, "abstract": "In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.", "doi": "10.1038/s41467-019-12283-6", "pmid": "31673082", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC6823371"}, {"db": "pii", "key": "10.1038/s41467-019-12283-6"}], "notes": [], "created": "2019-11-28T07:41:34.797Z", "modified": "2023-06-19T13:09:10.356Z"}]}