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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": "feb48652b3a64f24ab3cc30b33e698ab", "links": {"self": {"href": "https://publications.scilifelab.se/publication/feb48652b3a64f24ab3cc30b33e698ab.json"}, "display": {"href": "https://publications.scilifelab.se/publication/feb48652b3a64f24ab3cc30b33e698ab"}}, "title": "Genome-wide analysis identifies genetic effects on reproductive success and ongoing natural selection at the FADS locus.", "authors": [{"family": "Mathieson", "given": "Iain", "initials": "I", "orcid": "0000-0002-4256-3982", "researcher": {"href": "https://publications.scilifelab.se/researcher/ea771b602668431abd1a375ea66c46a6.json"}}, {"family": "Day", "given": "Felix R", "initials": "FR", "orcid": "0000-0003-3789-7651", "researcher": {"href": "https://publications.scilifelab.se/researcher/5d9ffc4d251a4469bcb97dd24dcc4218.json"}}, {"family": "Barban", "given": "Nicola", "initials": "N"}, {"family": "Tropf", "given": "Felix C", "initials": "FC"}, {"family": "Brazel", "given": "David M", "initials": "DM"}, {"family": "eQTLGen Consortium", "given": "", "initials": ""}, {"family": "BIOS Consortium", "given": "", "initials": ""}, {"family": "Vaez", "given": "Ahmad", "initials": "A", "orcid": "0000-0001-9048-3795", "researcher": {"href": "https://publications.scilifelab.se/researcher/34a09aa88bc74e1285ddd71655dbddc3.json"}}, {"family": "van Zuydam", 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"https://publications.scilifelab.se/researcher/e9276827839a4f3cb50dcaa2ad4708a5.json"}}, {"family": "den Hoed", "given": "Marcel", "initials": "M", "orcid": "0000-0001-8081-428X", "researcher": {"href": "https://publications.scilifelab.se/researcher/d712cc087d344b15ab9a7971640acebe.json"}}, {"family": "Ong", "given": "Ken K", "initials": "KK", "orcid": "0000-0003-4689-7530", "researcher": {"href": "https://publications.scilifelab.se/researcher/abdc034f3fa1428d9311a306a5446b35.json"}}, {"family": "Mills", "given": "Melinda C", "initials": "MC", "orcid": "0000-0003-1704-0001", "researcher": {"href": "https://publications.scilifelab.se/researcher/957f1b6833c64bbcb286e383512bc14b.json"}}, {"family": "Perry", "given": "John R B", "initials": "JRB", "orcid": "0000-0001-6483-3771", "researcher": {"href": "https://publications.scilifelab.se/researcher/39d95b143f6849b1b914bca9563218c8.json"}}], "type": "journal article", "published": "2023-03-02", "journal": {"title": "Nat Hum Behav", "issn": "2397-3374", "issn-l": null}, "abstract": "Identifying genetic determinants of reproductive success may highlight mechanisms underlying fertility and identify alleles under present-day selection. Using data in 785,604 individuals of European ancestry, we identified 43 genomic loci associated with either number of children ever born (NEB) or childlessness. These loci span diverse aspects of reproductive biology, including puberty timing, age at first birth, sex hormone regulation, endometriosis and age at menopause. Missense variants in ARHGAP27 were associated with higher NEB but shorter reproductive lifespan, suggesting a trade-off at this locus between reproductive ageing and intensity. Other genes implicated by coding variants include PIK3IP1, ZFP82 and LRP4, and our results suggest a new role for the melanocortin 1 receptor (MC1R) in reproductive biology. As NEB is one component of evolutionary fitness, our identified associations indicate loci under present-day natural selection. Integration with data from historical selection scans highlighted an allele in the FADS1/2 gene locus that has been under selection for thousands of years and remains so today. Collectively, our findings demonstrate that a broad range of biological mechanisms contribute to reproductive success.", "doi": "10.1038/s41562-023-01528-6", "pmid": "36864135", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service", "NGI SNP genotyping": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41562-023-01528-6"}], "notes": [], "created": "2023-04-06T13:50:09.776Z", "modified": "2023-04-06T13:50:10.709Z"}, {"entity": "publication", "iuid": "e389be71822d45d6ac04d848bfb48df6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e389be71822d45d6ac04d848bfb48df6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e389be71822d45d6ac04d848bfb48df6"}}, "title": "The power of genetic diversity in genome-wide association studies of lipids.", "authors": [{"family": "Graham", "given": "Sarah E", "initials": "SE", "orcid": "0000-0003-1271-2489", "researcher": {"href": 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"initials": "CJ"}, {"family": "Gaziano", "given": "John M", "initials": "JM"}, {"family": "Wilson", "given": "Peter", "initials": "P"}, {"family": "Rotimi", "given": "Charles N", "initials": "CN", "orcid": "0000-0001-5759-053X", "researcher": {"href": "https://publications.scilifelab.se/researcher/7fa2951fdebf4fddaad296d49b8f3f2b.json"}}, {"family": "Hazelhurst", "given": "Scott", "initials": "S"}, {"family": "Ramsay", "given": "Mich\u00e8le", "initials": "M", "orcid": "0000-0002-4156-4801", "researcher": {"href": "https://publications.scilifelab.se/researcher/31f970ff8b574a2290447b9626411d63.json"}}, {"family": "Trembath", "given": "Richard C", "initials": "RC"}, {"family": "van Heel", "given": "David A", "initials": "DA", "orcid": "0000-0002-0637-2265", "researcher": {"href": "https://publications.scilifelab.se/researcher/487906b4266443eab6fbe65e942bb5fe.json"}}, {"family": "Tamiya", "given": "Gen", "initials": "G"}, {"family": "Yamamoto", "given": "Masayuki", "initials": "M", "orcid": "0000-0002-9073-9436", "researcher": {"href": "https://publications.scilifelab.se/researcher/c566d57cdf9b43498cd9583fbb6c4c73.json"}}, {"family": "Kim", "given": "Bong-Jo", "initials": "BJ"}, {"family": "Mohlke", "given": "Karen L", "initials": "KL", "orcid": "0000-0001-6721-153X", "researcher": {"href": "https://publications.scilifelab.se/researcher/7c11d7ab911243edb9e2696efd95ecd4.json"}}, {"family": "Frayling", "given": "Timothy M", "initials": "TM"}, {"family": "Hirschhorn", "given": "Joel N", "initials": "JN", "orcid": "0000-0002-1650-7901", "researcher": {"href": "https://publications.scilifelab.se/researcher/79e3bb42733c4904a4543cb3b6397c0f.json"}}, {"family": "Kathiresan", "given": "Sekar", "initials": "S"}, {"family": "VA Million Veteran Program", "given": "", "initials": ""}, {"family": "Global Lipids Genetics Consortium*", "given": "", "initials": ""}, {"family": "Boehnke", "given": "Michael", "initials": "M", "orcid": "0000-0002-6442-7754", "researcher": {"href": "https://publications.scilifelab.se/researcher/b8cb72bdcea4492199a1b9d8ac406ac7.json"}}, {"family": "Natarajan", "given": "Pradeep", "initials": "P"}, {"family": "Peloso", "given": "Gina M", "initials": "GM", "orcid": "0000-0002-5355-8636", "researcher": {"href": "https://publications.scilifelab.se/researcher/3a0c07ebec3741efa6ef71d416e7c66a.json"}}, {"family": "Brown", "given": "Christopher D", "initials": "CD"}, {"family": "Morris", "given": "Andrew P", "initials": "AP", "orcid": "0000-0002-6805-6014", "researcher": {"href": "https://publications.scilifelab.se/researcher/991fd686a4a040a1a197c1f32d5b731b.json"}}, {"family": "Assimes", "given": "Themistocles L", "initials": "TL", "orcid": "0000-0003-2349-0009", "researcher": {"href": "https://publications.scilifelab.se/researcher/9e155ca3dd01486580be888d1ded405c.json"}}, {"family": "Deloukas", "given": "Panos", "initials": "P", "orcid": "0000-0001-9251-070X", "researcher": {"href": "https://publications.scilifelab.se/researcher/eb59dbd2f2204d41b801c41188611a9e.json"}}, {"family": "Sun", "given": "Yan V", "initials": "YV", "orcid": "0000-0002-2838-1824", "researcher": {"href": "https://publications.scilifelab.se/researcher/c6299caf6b6342fdbfab4c0d9738b28f.json"}}, {"family": "Willer", "given": "Cristen J", "initials": "CJ", "orcid": "0000-0001-5645-4966", "researcher": {"href": "https://publications.scilifelab.se/researcher/b3a8e1d33146452b87e7e21eb5339f80.json"}}], "type": "journal article", "published": "2021-12-00", "journal": {"title": "Nature", "issn": "1476-4687", "volume": "600", "issue": "7890", "pages": "675-679", "issn-l": "0028-0836"}, "abstract": "Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use1. Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels2, heart disease remains the leading cause of death worldwide3. Genome-wideassociation studies (GWAS) of blood lipid levels have led to important biological and clinical insights, as well as new drug targets, for cardiovascular disease. However, most previous GWAS4-23 have been conducted in European ancestry populations and may have missed genetic variants that contribute to lipid-level variation in other ancestry groups. These include differences in allele frequencies, effect sizes and linkage-disequilibrium patterns24. Here we conduct a multi-ancestry, genome-wide genetic discovery meta-analysis of lipid levels in approximately 1.65 million individuals, including 350,000 of non-European ancestries. We quantify the gain in studying non-European ancestries and provide evidence to support the expansion of recruitment of additional ancestries, even with relatively small sample sizes. We find that increasing diversity rather than studying additional individuals of European ancestry results in substantial improvements in fine-mapping functional variants and portability of polygenic prediction (evaluated in approximately 295,000 individuals from 7 ancestry groupings). Modest gains in the number of discovered loci and ancestry-specific variants were also achieved. As GWAS expand emphasis beyond the identification of genes and fundamental biology towards the use of genetic variants for preventive and precision medicine25, we anticipate that increased diversity of participants will lead to more accurate and equitable26 application of polygenic scores in clinical practice.", "doi": "10.1038/s41586-021-04064-3", "pmid": "34887591", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "mid", "key": "NIHMS1758809"}, {"db": "pmc", "key": "PMC8730582"}, {"db": "pii", "key": "10.1038/s41586-021-04064-3"}], "notes": [], "created": "2021-12-22T19:39:50.082Z", "modified": "2023-06-19T12:31:07.699Z"}, {"entity": "publication", "iuid": "48f74c2afc0b4af8befb22016e4d7b0c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/48f74c2afc0b4af8befb22016e4d7b0c.json"}, "display": {"href": 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"researcher": {"href": "https://publications.scilifelab.se/researcher/19f5ce9936ca454c85f0af966acac5c0.json"}}, {"family": "Hofman", "given": "Albert", "initials": "A"}, {"family": "Munroe", "given": "Patricia B", "initials": "PB", "orcid": "0000-0002-4176-2947", "researcher": {"href": "https://publications.scilifelab.se/researcher/657544a7f921459f926aae5cd0e2065c.json"}}, {"family": "Gudnason", "given": "Vilmundur", "initials": "V", "orcid": "0000-0001-5696-0084", "researcher": {"href": "https://publications.scilifelab.se/researcher/d18327939c1541acba054b2340ac174f.json"}}, {"family": "Siscovick", "given": "David S", "initials": "DS"}, {"family": "Watkins", "given": "Hugh", "initials": "H"}, {"family": "Lecoeur", "given": "Cecile", "initials": "C", "orcid": "0000-0003-0075-6417", "researcher": {"href": "https://publications.scilifelab.se/researcher/f6abf12d60c24032a1c2b315904b0721.json"}}, {"family": "Vollenweider", "given": "Peter", "initials": "P"}, {"family": "Franco-Cereceda", "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"}]}