Genetic predisposition to mosaic Y chromosome loss in blood
Autor: | Ragnar P. Kristjansson, Steven A. McCarroll, Florian Zink, Malcolm G. Dunlop, Nicholas J. Wareham, Yoichiro Kamatani, Daniel F. Gudbjartsson, Giulio Genovese, Rong Li, Stephen J. Chanock, Unnur Thorsteinsdottir, Ben Kinnersley, Kari Stefansson, Philip J. Law, Martin Ingelsson, Lars Forsberg, Joe Dennis, Richard S. Houlston, Jonatan Halvardson, Nicola D. Kerrison, Chikashi Terao, Douglas F. Easton, Anna Murray, Yunxuan Jiang, Jan P. Dumanski, Chey Loveday, Steve P Jackson, Robert A. Scott, Edyta Rychlicka-Buniowska, Ian Tomlinson, Daniel J Wright, Deborah J. Thompson, Victoria A Fisher, Yoshinori Murakami, John R. B. Perry, Paweł Olszewski, Felix R. Day, Eva Hoffmann, Hanna Davies, Po-Ru Loh, Adam Auton, Siddhartha Kar, Behrooz Torabi Moghadam, Clare Turnbull, Ken K. Ong, Marcus Danielsson, Jacob C. Ulirsch, Jonas Mattisson, Patrick Sulem, Olafur B. Davidsson, Mitchell J. Machiela |
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Přispěvatelé: | Internal Medicine, APH - Methodology, APH - Mental Health, Biological Psychology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases |
Rok vydání: | 2019 |
Předmět: |
Male
0301 basic medicine Haematopoietic system Genome-wide association study Chromosomes Human Y/genetics Genome-wide association studies 0302 clinical medicine Y Chromosome Neoplasms Databases Genetic Leukocytes Cancer genomics Genetics Multidisciplinary Mosaicism Genetic Predisposition to Disease/genetics Leukocytes/pathology Middle Aged Neoplasms/genetics 3. Good health 030220 oncology & carcinogenesis Medical genetics Female Chromosome Deletion Human Genetic Markers Adult Genomic instability medicine.medical_specialty Cell division Y/genetics Biology Y chromosome Article Genomic Instability Chromosomes Databases 03 medical and health sciences Genetic medicine Genetic predisposition Humans Genetic Predisposition to Disease Gene Aged Genetic Markers/genetics Chromosomes Human Y Computational Biology Cancer Chromosome medicine.disease United Kingdom 030104 developmental biology Genetic marker Genomic Instability/genetics |
Zdroj: | Thompson, D J, Genovese, G, Kar, S, Perry, J RB & et al. 2019, ' Genetic predisposition to mosaic Y chromosome loss in blood ', Nature, vol. 575, pp. 652–657 . https://doi.org/10.1038/s41586-019-1765-3 Nature, 575(7784), 652-657. Nature Publishing Group Thompson, D J, Genovese, G, Forsberg, L A, Perry, J R B, International Lung Cancer Consortium (INTEGRAL-ILCCO), Boomsma, D, Nivard, M, van Dongen, J, Pool, R & Hottenga, J J 2019, ' Genetic predisposition to mosaic Y chromosome loss in blood ', Nature, vol. 575, no. 7784, pp. 652-657 . https://doi.org/10.1038/s41586-019-1765-3 Nature 2019, ' Genetic predisposition to mosaic Y chromosome loss in blood ', Nature, vol. 575, no. 7784, pp. 652-657 . https://doi.org/10.1038/s41586-019-1765-3 Thompson, D J, Genovese, G, Halvardson, J, Ulirsch, J C, Wright, D J, Terao, C, Davidsson, O B, Day, F R, Sulem, P, Jiang, Y, Danielsson, M, Davies, H, Dennis, J, Dunlop, M G, Easton, D F, Fisher, V A, Zink, F, Houlston, R S, Ingelsson, M, Kar, S, Kerrison, N D, Kinnersley, B, Kristjansson, R P, Law, P J, Li, R, Loveday, C, Mattisson, J, McCarroll, S A, Murakami, Y, Murray, A, Olszewski, P, Rychlicka-Buniowska, E, Scott, R A, Thorsteinsdottir, U, Tomlinson, I, Moghadam, B T, Turnbull, C, Wareham, N J, Gudbjartsson, D F, Kamatani, Y, Hoffmann, E R, Jackson, S P, Stefansson, K, Auton, A, Ong, K K, Machiela, M J, Loh, P-R, Dumanski, J P, Chanock, S J, Forsberg, L A, International Lung Cancer Consortium (INTEGRAL-ILCCO) & The PRACTICAL Consortium 2019, ' Genetic predisposition to mosaic Y chromosome loss in blood ', Nature, vol. 575, no. 7784, pp. 652-657 . https://doi.org/10.1038/s41586-019-1765-3 |
ISSN: | 1476-4687 0028-0836 |
Popis: | Mosaic loss of chromosome Y (LOY) in circulating white blood cells is the most common form of clonal mosaicism1–5, yet our knowledge of the causes and consequences of this is limited. Here, using a computational approach, we estimate that 20% of the male population represented in the UK Biobank study (n = 205,011) has detectable LOY. We identify 156 autosomal genetic determinants of LOY, which we replicate in 757,114 men of European and Japanese ancestry. These loci highlight genes that are involved in cell-cycle regulation and cancer susceptibility, as well as somatic drivers of tumour growth and targets of cancer therapy. We demonstrate that genetic susceptibility to LOY is associated with non-haematological effects on health in both men and women, which supports the hypothesis that clonal haematopoiesis is a biomarker of genomic instability in other tissues. Single-cell RNA sequencing identifies dysregulated expression of autosomal genes in leukocytes with LOY and provides insights into why clonal expansion of these cells may occur. Collectively, these data highlight the value of studying clonal mosaicism to uncover fundamental mechanisms that underlie cancer and other ageing-related diseases. A genome-wide association study of mosaic loss of chromosome Y (LOY) in UK Biobank participants identifies 156 genetic determinants of LOY, showing that LOY is associated with cancer and non-haematological health outcomes. |
Databáze: | OpenAIRE |
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