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
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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