Chen Li, Svetlana Stoma, Luca A. Lotta, Sophie Warner, Eva Albrecht, Alessandra Allione, Pascal P. Arp, Linda Broer, Jessica L. Buxton, Heiner Boeing, Claudia Langenberg, Veryan Codd
- Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1 , PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findingsLeukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1 , PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.…
MetadatenAuthor details: | Chen LiORCiD, Svetlana StomaORCiD, Luca A. LottaORCiD, Sophie Warner, Eva Albrecht, Alessandra AllioneORCiD, Pascal P. Arp, Linda BroerORCiD, Jessica L. Buxton, Heiner BoeingORCiDGND, Claudia LangenbergORCiDGND, Veryan CoddORCiD |
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URN: | urn:nbn:de:kobv:517-opus4-526843 |
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DOI: | https://doi.org/10.25932/publishup-52684 |
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ISSN: | 1866-8372 |
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Title of parent work (German): | Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe |
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Publication series (Volume number): | Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe (1205) |
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Publication type: | Postprint |
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Language: | English |
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Date of first publication: | 2019/10/22 |
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Publication year: | 2020 |
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Publishing institution: | Universität Potsdam |
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Release date: | 2021/11/17 |
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Tag: | Mendelian randomization; cancer; database; disease; genes; gwas; heart; loci; risk; variants |
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Issue: | 3 |
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Number of pages: | 18 |
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Source: | The American Journal of Human Genetics, Volume 106, Issue 3, 2020, Pages 389-404, ISSN 0002-9297, https://doi.org/10.1016/j.ajhg.2020.02.006 |
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Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Ernährungswissenschaft |
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DDC classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
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Peer review: | Referiert |
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Publishing method: | Open Access / Green Open-Access |
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License (German): | CC-BY - Namensnennung 4.0 International |
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External remark: | Bibliographieeintrag der Originalveröffentlichung/Quelle |
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