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DIALOY SIGNED

Mosaic loss of chromosome Y (LOY) in blood cells - a new biomarker for risk of cancer and Alzheimer’s disease in men

Total Cost €

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EC-Contrib. €

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Partnership

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Project "DIALOY" data sheet

The following table provides information about the project.

Coordinator
UPPSALA UNIVERSITET 

Organization address
address: VON KRAEMERS ALLE 4
city: UPPSALA
postcode: 751 05
website: www.uu.se

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Sweden [SE]
 Project website http://www.forsberglab.com
 Total cost 1˙525˙000 €
 EC max contribution 1˙525˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-STG
 Funding Scheme ERC-STG
 Starting year 2016
 Duration (year-month-day) from 2016-03-01   to  2021-02-28

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UPPSALA UNIVERSITET SE (UPPSALA) coordinator 1˙525˙000.00

Map

 Project objective

My recent discoveries show that mosaic loss of chromosome Y (LOY) in peripheral blood is associated with increased risks of cancer and Alzheimer’s disease (AD). These conditions are responsible for >50% of morbidity/mortality in aging men. More than 15% of men older than 70 show some degree of LOY and these men survive on average only half as long as men without LOY. Smoking is strongly associated with LOY and remarkably, the fraction of cells with LOY decreases after cessation of smoking. Cells with LOY can be detected, and disease risks predicted, many years before clinical manifestation of disease. These results of associations between LOY, cancer and smoking have been published in Nature Genetics and Science during 2014.

The overall objective of the proposal is to develop LOY as a new, strong and predictive biomarker. To this end, the research program focuses on three objectives: 1) expanding the study of LOY and associations with disease risks in still larger cohorts; 2) investigating functional aspects of LOY; and 3) develop improved technology for LOY-detection. The successful execution of the project is essential before LOY-testing in clinics can be realized.

Diagnosis of cancer and AD in modern medicine is based on clinical symptoms of disease. Through earlier identification of individuals at increased risk for disease, preventive strategies could be applied, before the severe stages appear. Preliminary results affirm the feasibility of the project and provide proof-of-concept that LOY-tests can be used for early identification of men with increased risks for these diseases. In addition to improving diagnostics and therapeutics; implementation of LOY-testing could prevent smoking-related disease and reduce the health care costs. In the end, LOY-testing could decrease male mortality rates and possibly eliminate the sex-difference in life expectancy. The project will therefore benefit individual patients as well as healthcare systems and society at large.

 Publications

year authors and title journal last update
List of publications.
2018 Lars A. Forsberg
Back to the drawing board—loss of chromosome Y (LOY) in leukocytes is associated with age-related macular degeneration
published pages: , ISSN: 1018-4813, DOI: 10.1038/s41431-018-0261-9
European Journal of Human Genetics 2019-10-08
2018 Lars A. Forsberg, Jonatan Halvardson, Edyta Rychlicka-Buniowska, Marcus Danielsson, Behrooz Torabi Moghadam, Jonas Mattisson, Chiara Rasi, Hanna Davies, Lars Lind, Vilmantas Giedraitis, Lars Lannfelt, Lena Kilander, Martin Ingelsson and Jan P. Dumanski
Mosaic loss of chromosome Y in leukocytes matters
published pages: , ISSN: 1061-4036, DOI: 10.1038/s41588-018-0267-9
Nature Genetics 2019-10-08
2019 Deborah Thompson, Giulio Genovese, Jonatan Halvardson, Jacob Ulirsch, Daniel Wright, Chikashi Terao, Olafur Davidsson, Felix Day, Patrick Sulem, Yunxuan Jiang, Marcus Danielsson, Hanna Davies, Joe Dennis, Malcolm Dunlop, Douglas Easton, Victoria Fisher, Florian Zink, Richard Houlston, Martin Ingelsson, Siddhartha Kar, Nicola Kerrison, Ragnar Kristjansson, Rong Li, Chey Loveday, Jonas Mattisson, Steven McCarroll, Yoshinori Murakami, Anna Murray, Pawel Olszewski, Edyta Rychlicka-Buniowska, Robert Scott, Unnur Thorsteinsdottir, Ian Tomlinson, Behrooz Torabi Moghadam, Clare Turnbull, Nicholas Wareham, Daniel Gudbjartsson, INTEGRAL-ILCCO, The Breast Cancer Association Consortium, CIMBA, The Endometrial Cancer Association Consortium, The Ovarian Cancer Association Consortium, The PRACTICAL Consortium, The Kidney Cancer GWAS Meta-Analysis Project, eQTLGen Consortium, BIOS Consortium, 23andMe Research Team, Yoichiro Kamatani, Hilary Finucane, Eva Hoffmann, Steve Jackson, Kari Stefansson, Adam Auton, Ken Ong, Mitchell Machiela, Po-Ru Loh, Jan Dumanski, Stephen Chanock, Lars Forsberg, John Perry
Genetic predisposition to mosaic Y chromosome loss in blood is associated with genomic instability in other tissues and susceptibility to non-haematological cancers
published pages: , ISSN: , DOI: 10.1101/514026
2019-05-22
2016 Lars A. Forsberg, David Gisselsson, Jan P. Dumanski
Mosaicism in health and disease — clones picking up speed
published pages: 128-142, ISSN: 1471-0056, DOI: 10.1038/nrg.2016.145
Nature Reviews Genetics 18/2 2019-06-19
2016 Jan P. Dumanski, Jean-Charles Lambert, Chiara Rasi, Vilmantas Giedraitis, Hanna Davies, Benjamin Grenier-Boley, Cecilia M. Lindgren, Dominique Campion, Carole Dufouil, Florence Pasquier, Philippe Amouyel, Lars Lannfelt, Martin Ingelsson, Lena Kilander, Lars Lind, Lars A. Forsberg
Mosaic Loss of Chromosome Y in Blood Is Associated with Alzheimer Disease
published pages: 1208-1219, ISSN: 0002-9297, DOI: 10.1016/j.ajhg.2016.05.014
The American Journal of Human Genetics 98/6 2019-06-19
2017 Lars A. Forsberg
Loss of chromosome Y (LOY) in blood cells is associated with increased risk for disease and mortality in aging men
published pages: 657-663, ISSN: 0340-6717, DOI: 10.1007/s00439-017-1799-2
Human Genetics 136/5 2019-06-19
2017 Jan P. Dumanski, Johan Sundström, Lars A. Forsberg
Loss of Chromosome Y in Leukocytes and Major Cardiovascular Events
published pages: e001820, ISSN: 1942-3268, DOI: 10.1161/CIRCGENETICS.117.001820
Circulation: Cardiovascular Genetics 10/4 2019-06-19

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