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"https://publications-affiliated.scilifelab.se/researcher/a1901e08f989434fb01dfa17b0a85470.json"}}, {"family": "Libby", "given": "Peter", "initials": "P", "orcid": "0000-0002-1502-502X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/39fb20acff0442bd92fc7931d3ee6cf9.json"}}, {"family": "Ellinor", "given": "Patrick T", "initials": "PT", "orcid": "0000-0002-2067-0533", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fd1830794e884e6e849fd4f7645c9b61.json"}}, {"family": "Pankratz", "given": "Nathan", "initials": "N", "orcid": "0000-0001-5958-693X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ad5e6b749b264d1e83ea58d5bce6c88e.json"}}, {"family": "Ebert", "given": "Benjamin L", "initials": "BL", "orcid": "0000-0003-0197-5451", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/56e4f1c53a4348e2b0ceb44a38850a17.json"}}, {"family": "Reiner", "given": "Alexander P", "initials": "AP"}, {"family": "Mathias", "given": "Rasika A", "initials": "RA", "orcid": "0000-0002-2282-9042", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/71dfe469451f4573bcccc96f981f7915.json"}}, {"family": "Do", "given": "Ron", "initials": "R", "orcid": "0000-0002-3144-3627", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4ab0c452994042219ca6120d45e72604.json"}}, {"family": "NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium", "given": "", "initials": ""}, {"family": "Natarajan", "given": "Pradeep", "initials": "P", "orcid": "0000-0001-8402-7435", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fe8bd48c61c047cd8e61c35d9e9ac650.json"}}], "type": "journal article", "published": "2022-04-08", "journal": {"title": "Sci Adv", "issn": "2375-2548", "volume": "8", "issue": "14", "pages": "eabl6579", "issn-l": "2375-2548"}, "abstract": "Human genetic studies support an inverse causal relationship between leukocyte telomere length (LTL) and coronary artery disease (CAD), but directionally mixed effects for LTL and diverse malignancies. Clonal hematopoiesis of indeterminate potential (CHIP), characterized by expansion of hematopoietic cells bearing leukemogenic mutations, predisposes both hematologic malignancy and CAD. TERT (which encodes telomerase reverse transcriptase) is the most significantly associated germline locus for CHIP in genome-wide association studies. Here, we investigated the relationship between CHIP, LTL, and CAD in the Trans-Omics for Precision Medicine (TOPMed) program (n = 63,302) and UK Biobank (n = 47,080). Bidirectional Mendelian randomization studies were consistent with longer genetically imputed LTL increasing propensity to develop CHIP, but CHIP then, in turn, hastens to shorten measured LTL (mLTL). We also demonstrated evidence of modest mediation between CHIP and CAD by mLTL. Our data promote an understanding of potential causal relationships across CHIP and LTL toward prevention of CAD.", "doi": "10.1126/sciadv.abl6579", "pmid": "35385311", "labels": {"Abhishek Niroula": null, "DDLS Fellow": null}, "xrefs": [{"db": "pmc", "key": "PMC8986098"}], "notes": [], "created": "2023-11-20T11:36:14.966Z", "modified": "2023-11-20T11:36:17.765Z"}, {"entity": "publication", "iuid": "61e8816e8d6e421dbf1ee3ee3e0fb89c", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/61e8816e8d6e421dbf1ee3ee3e0fb89c.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/61e8816e8d6e421dbf1ee3ee3e0fb89c"}}, "title": "The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study.", "authors": [{"family": "Winkler", "given": "Thomas W", "initials": "TW"}, {"family": "Justice", "given": "Anne E", "initials": "AE"}, {"family": "Graff", "given": "Mariaelisa", 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{"family": "Abecasis", "given": "Goncalo R", "initials": "GR"}, {"family": "Assimes", "given": "Themistocles L", "initials": "TL", "orcid": "0000-0003-2349-0009", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/610f47c94b0c4fe2bb2da6921aa8a1ef.json"}}, {"family": "Barroso", "given": "In\u00eas", "initials": "I"}, {"family": "Berndt", "given": "Sonja I", "initials": "SI"}, {"family": "Boehnke", "given": "Michael", "initials": "M"}, {"family": "Deloukas", "given": "Panos", "initials": "P", "orcid": "0000-0001-9251-070X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d034d0cd32a84b959bd29f8ef8c91979.json"}}, {"family": "Fox", "given": "Caroline S", "initials": "CS"}, {"family": "Groop", "given": "Leif C", "initials": "LC"}, {"family": "Hunter", "given": "David J", "initials": "DJ"}, {"family": "Ingelsson", "given": "Erik", "initials": "E"}, {"family": "Kaplan", "given": "Robert C", "initials": "RC"}, {"family": "McCarthy", "given": "Mark I", "initials": "MI"}, {"family": "Mohlke", "given": "Karen L", "initials": "KL"}, {"family": "O'Connell", "given": "Jeffrey R", "initials": "JR"}, {"family": "Schlessinger", "given": "David", "initials": "D"}, {"family": "Strachan", "given": "David P", "initials": "DP"}, {"family": "Stefansson", "given": "Kari", "initials": "K", "orcid": "0000-0003-1676-864X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9edf80871ac84e76a4d1316fc7079d7d.json"}}, {"family": "van Duijn", "given": "Cornelia M", "initials": "CM"}, {"family": "Hirschhorn", "given": "Joel N", "initials": "JN"}, {"family": "Lindgren", "given": "Cecilia M", "initials": "CM"}, {"family": "Heid", "given": "Iris M", "initials": "IM"}, {"family": "North", "given": "Kari E", "initials": "KE", "orcid": "0000-0002-8903-0366", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d43affb5fa064e0d98d5b6e5cd017461.json"}}, {"family": "Borecki", "given": "Ingrid B", "initials": "IB"}, {"family": "Kutalik", "given": "Zolt\u00e1n", "initials": "Z", "orcid": "0000-0001-8285-7523", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e566b994d65a4365b224cd4ae369827a.json"}}, {"family": "Loos", "given": "Ruth J F", "initials": "RJ", "orcid": "0000-0002-8532-5087", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/179eb6511eba4d33b633599c5652e344.json"}}], "type": "journal article", "published": "2015-10-00", "journal": {"title": "PLoS Genet", "issn": "1553-7404", "volume": "11", "issue": "10", "pages": "e1005378", "issn-l": "1553-7390"}, "abstract": "Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men \u226450y, men >50y, women \u226450y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR<5%) age-specific effects, of which 11 had larger effects in younger (<50y) than in older adults (\u226550y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may provide further insights into the biology that underlies weight change with age or the sexually dimorphism of body shape. ", "doi": "10.1371/journal.pgen.1005378", "pmid": "26426971", "labels": {"Affiliated researcher": null}, "xrefs": [{"db": "pii", "key": "PGENETICS-D-14-03117"}, {"db": "pmc", "key": "PMC4591371"}], "notes": [], "created": "2018-12-05T08:45:37.291Z", "modified": "2025-11-30T11:22:50.301Z"}]}