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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": "20044ca7f045473daf17863e0344b451", "links": {"self": {"href": "https://publications.scilifelab.se/publication/20044ca7f045473daf17863e0344b451.json"}, "display": {"href": "https://publications.scilifelab.se/publication/20044ca7f045473daf17863e0344b451"}}, "title": "Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals.", "authors": [{"family": "Winkler", "given": "Thomas W", "initials": "TW", "orcid": "0000-0003-0292-5421", 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"0000-0003-2544-4460", "researcher": {"href": "https://publications.scilifelab.se/researcher/b6b229457c2c4b25ae9c7d2cf029b82b.json"}}, {"family": "Gao", "given": "Xin", "initials": "X"}, {"family": "Sim", "given": "Xueling", "initials": "X", "orcid": "0000-0002-1233-7642", "researcher": {"href": "https://publications.scilifelab.se/researcher/3216a8d2a7264a1390a886fa09d5d648.json"}}, {"family": "Wang", "given": "Ya Xing", "initials": "YX", "orcid": "0000-0003-2749-7793", "researcher": {"href": "https://publications.scilifelab.se/researcher/a335d5361052470689def030e03e597b.json"}}, {"family": "Friedlander", "given": "Yechiel", "initials": "Y"}, {"family": "Tham", "given": "Yih-Chung", "initials": "YC", "orcid": "0000-0002-6752-797X", "researcher": {"href": "https://publications.scilifelab.se/researcher/8175b4e810bb4a1b9448d2e69be60a31.json"}}, {"family": "Kamatani", "given": "Yoichiro", "initials": "Y", "orcid": "0000-0001-8748-5597", "researcher": {"href": "https://publications.scilifelab.se/researcher/6cf00b09991c4b40bd77a4f2c5bfad97.json"}}, {"family": "Okada", "given": "Yukinori", "initials": "Y", "orcid": "0000-0002-0311-8472", "researcher": {"href": "https://publications.scilifelab.se/researcher/40b13860bfef41959c29be2de853b456.json"}}, {"family": "Milaneschi", "given": "Yuri", "initials": "Y"}, {"family": "Yu", "given": "Zhi", "initials": "Z", "orcid": "0000-0003-4810-3474", "researcher": {"href": "https://publications.scilifelab.se/researcher/df8600142a4249b6860fd0cbfa3bda5c.json"}}, {"family": "Lifelines cohort study", "given": "", "initials": ""}, {"family": "DiscovEHR/MyCode study", "given": "", "initials": ""}, {"family": "VA Million Veteran Program", "given": "", "initials": ""}, {"family": "Stark", "given": "Klaus J", "initials": "KJ"}, {"family": "Stefansson", "given": "Kari", "initials": "K", "orcid": "0000-0003-1676-864X", "researcher": {"href": "https://publications.scilifelab.se/researcher/679465193fba4887a68e2aec34ccfd8e.json"}}, {"family": "B\u00f6ger", "given": "Carsten A", "initials": "CA"}, {"family": "Hung", "given": "Adriana M", "initials": "AM"}, {"family": "Kronenberg", "given": "Florian", "initials": "F", "orcid": "0000-0003-2229-1120", "researcher": {"href": "https://publications.scilifelab.se/researcher/ebc59079554842ecb3512ef90249a2f2.json"}}, {"family": "K\u00f6ttgen", "given": "Anna", "initials": "A", "orcid": "0000-0002-4671-3714", "researcher": {"href": "https://publications.scilifelab.se/researcher/fe4cb85a14da4db6bc932a8bc4148efb.json"}}, {"family": "Pattaro", "given": "Cristian", "initials": "C", "orcid": "0000-0002-4119-0109", "researcher": {"href": "https://publications.scilifelab.se/researcher/3a6a570bbec647b188c4a7a5da03caac.json"}}, {"family": "Heid", "given": "Iris M", "initials": "IM", "orcid": "0000-0002-4122-5308", "researcher": {"href": "https://publications.scilifelab.se/researcher/34990140a9604dd7b61807dafc8fabc6.json"}}], "type": "journal article", "published": "2022-06-13", "journal": {"title": "Commun Biol", "issn": "2399-3642", "volume": "5", "issue": "1", "pages": "580", "issn-l": "2399-3642"}, "abstract": "Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (nDM = 178,691, nnoDM = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.", "doi": "10.1038/s42003-022-03448-z", "pmid": "35697829", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "NGI SNP genotyping": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s42003-022-03448-z"}, {"db": "pmc", "key": "PMC9192715"}], "notes": [], "created": "2022-06-14T13:16:22.813Z", "modified": "2022-11-21T15:40:40.440Z"}, {"entity": "publication", "iuid": "63da0d7704a9479ca62f9eee3d3ffdf5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/63da0d7704a9479ca62f9eee3d3ffdf5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/63da0d7704a9479ca62f9eee3d3ffdf5"}}, "title": "Metabolomic and lipidomic assessment of the metabolic syndrome in Dutch middle-aged individuals reveals novel biological signatures separating health and disease.", "authors": [{"family": "Surowiec", "given": "Izabella", "initials": "I"}, {"family": "Noordam", "given": "Raymond", "initials": "R", "orcid": "0000-0001-7801-809X", "researcher": {"href": "https://publications.scilifelab.se/researcher/6eb07bec2aa54b5a9a661b8b6c431e7a.json"}}, {"family": "Bennett", "given": "Kate", "initials": "K"}, {"family": "Beekman", "given": "Marian", "initials": "M"}, {"family": "Slagboom", "given": "P Eline", "initials": "PE"}, {"family": "Lundstedt", "given": "Torbj\u00f6rn", "initials": "T"}, {"family": "van Heemst", "given": "Diana", "initials": "D"}], "type": "journal article", "published": "2019-02-12", "journal": {"title": "Metabolomics", "issn": "1573-3890", "volume": "15", "issue": "2", "pages": "23", "issn-l": "1573-3882"}, "abstract": "We aimed to identify novel metabolite and lipid signatures connected with the metabolic syndrome in a Dutch middle-aged population.\n\n115 individuals with a metabolic syndrome score ranging from 0 to 5 [50 cases of the metabolic syndrome (score \u2265 3) and 65 controls] were enrolled from the Leiden Longevity Study, and LC/GC-MS metabolomics and lipidomics profiling were performed on fasting plasma samples. Data were analysed with principal component analysis and orthogonal projections to latent structures (OPLS) to study metabolite/lipid signatures associated with the metabolic syndrome. In addition, univariate analyses were done with linear regression, adjusted for age and sex, for the study of individual metabolites/lipids in relation to the metabolic syndrome.\n\nData was available on 103 metabolites and 223 lipids. In the OPLS model with metabolic syndrome score (Y-variable), 9 metabolites were negatively correlated and 26 metabolites (mostly acylcarnitines, amino acids and keto acids) were positively correlated with the metabolic syndrome score. In addition, a total of 100 lipids (mainly triacylglycerides) were positively correlated and 10 lipids from different lipid classes were negatively correlated with the metabolic syndrome score. In the univariate analyses, the metabolic syndrome (score) was associated with multiple individual metabolites (e.g., valeryl carnitine, pyruvic acid, lactic acid, alanine) and lipids [e.g., diglyceride(34:1), diglyceride(36:2)].\n\nIn this first study on metabolomics/lipidomics of the metabolic syndrome, we identified multiple novel metabolite and lipid signatures, from different chemical classes, that were connected to the metabolic syndrome and are of interest to cardiometabolic disease biology.", "doi": "10.1007/s11306-019-1484-7", "pmid": "30830468", "labels": {"Swedish Metabolomics Centre": "Service"}, "xrefs": [{"db": "pii", "key": "10.1007/s11306-019-1484-7"}, {"db": "pmc", "key": "PMC6373335"}], "notes": [], "created": "2020-01-21T10:14:11.835Z", "modified": "2025-10-17T13:03:17.829Z"}]}