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"https://publications-affiliated.scilifelab.se/researcher/5b41e3ece7d3475c821424ec9e04fbd5.json"}}, {"family": "Riese", "given": "Harriette", "initials": "H"}, {"family": "Lehtim\u00e4ki", "given": "Terho", "initials": "T", "orcid": "0000-0002-2555-4427", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/74306ef9629647f7a0297b890df37cd0.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", "volume": "14", "issue": "1", "pages": "4646", "issn-l": "2041-1723"}, "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": [], "xrefs": [{"db": "pmc", "key": "PMC10397318"}, {"db": "pii", "key": "10.1038/s41467-023-39521-2"}], "notes": [], "created": "2026-09-23T09:01:39.863Z", "modified": "2026-09-23T09:01:42.602Z"}, {"entity": "publication", "iuid": "703b0318c565484ab513934b4b288f30", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/703b0318c565484ab513934b4b288f30.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/703b0318c565484ab513934b4b288f30"}}, "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": 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"https://publications-affiliated.scilifelab.se/researcher/4105b31d72044f76bfd07ca12a274569.json"}}, {"family": "Willemsen", "given": "Gonneke", "initials": "G"}, {"family": "Zhao", "given": "Jing Hau", "initials": "JH"}, {"family": "Zhao", "given": "Wei", "initials": "W", "orcid": "0000-0001-7388-0692", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4d4b5b8f14c041fd9481472c3254dff1.json"}}, {"family": "Zhao", "given": "Yajie", "initials": "Y", "orcid": "0000-0002-2747-0219", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/159377a0321440949635f7c40ac2fb25.json"}}, {"family": "Snieder", "given": "Harold", "initials": "H", "orcid": "0000-0003-1949-2298", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bb5a2135b774429596606e980c9268ec.json"}}, {"family": "den Hoed", "given": "Marcel", "initials": "M", "orcid": "0000-0001-8081-428X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1d3e34c06cff4446ad703cde901c5033.json"}}, {"family": "Ong", "given": "Ken K", "initials": "KK", "orcid": "0000-0003-4689-7530", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2fc9a3caa450429e9fe6b6dbeb5f0a44.json"}}, {"family": "Mills", "given": "Melinda C", "initials": "MC", "orcid": "0000-0003-1704-0001", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/78515e421046451c983d115b9bc4adfc.json"}}, {"family": "Perry", "given": "John R B", "initials": "JRB", "orcid": "0000-0001-6483-3771", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0985df254e574e5e8b7d783256c84ed7.json"}}], "type": "journal article", "published": "2023-05-00", "journal": {"title": "Nat Hum Behav", "issn": "2397-3374", "volume": "7", "issue": "5", "pages": "790-801", "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": [], "xrefs": [{"db": "pii", "key": "10.1038/s41562-023-01528-6"}], "notes": [], "created": "2026-09-23T08:38:43.054Z", "modified": "2026-09-23T08:38:44.809Z"}]}