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Mosaic Loss of Chro...
Mosaic Loss of Chromosome Y in Blood Is Associated with Alzheimer Disease
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- Dumanski, Jan P. (författare)
- Uppsala universitet,Medicinsk genetik och genomik,Science for Life Laboratory, SciLifeLab
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- Lambert, Jean-Charles (författare)
- Univ Lille, INSERM, CHU Lille, Pasteur Lille,U1167,RID AGE Risk Factors & Mol De, F-59000 Lille, France.
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- Rasi, Chiara (författare)
- Uppsala universitet,Medicinsk genetik och genomik,Science for Life Laboratory, SciLifeLab
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- Giedraitis, Vilmantas (författare)
- Uppsala universitet,Geriatrik
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- Davies, Hanna (författare)
- Uppsala universitet,Medicinsk genetik och genomik,Science for Life Laboratory, SciLifeLab
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- Grenier-Boley, Benjamin (författare)
- Univ Lille, INSERM, CHU Lille, Pasteur Lille,U1167,RID AGE Risk Factors & Mol De, F-59000 Lille, France.
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- Lindgren, Cecilia M. (författare)
- Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.;Broad Inst MIT, Cambridge, MA 02142 USA.;Harvard Univ, Cambridge, MA 02142 USA.
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- Campion, Dominique (författare)
- Rouen Univ Hosp, INSERM, CNR MAJ, U1079, F-76031 Rouen, France.
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- Dufouil, Carole (författare)
- Victor Segalen Univ, INSERM, U708, F-33076 Bordeaux, France.
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- Pasquier, Florence (författare)
- Univ Lille, CNR MAJ, Inserm 1171, F-59000 Lille, France.;CHU Lille, F-59000 Lille, France.
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- Amouyel, Philippe (författare)
- Univ Lille, INSERM, CHU Lille, Pasteur Lille,U1167,RID AGE Risk Factors & Mol De, F-59000 Lille, France.
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- Lannfelt, Lars (författare)
- Uppsala universitet,Geriatrik
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- Ingelsson, Martin (författare)
- Uppsala universitet,Geriatrik
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- Kilander, Lena (författare)
- Uppsala universitet,Geriatrik
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- Lind, Lars (författare)
- Uppsala universitet,Kardiovaskulär epidemiologi
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- Forsberg, Lars A. (författare)
- Uppsala universitet,Medicinsk genetik och genomik,Science for Life Laboratory, SciLifeLab
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(creator_code:org_t)
- Elsevier BV, 2016
- 2016
- Engelska.
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 98:6, s. 1208-1219
- Relaterad länk:
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https://uu.diva-port... (primary) (Raw object)
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http://www.cell.com/...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Men have a shorter life expectancy compared with women but the underlying factor(s) are not clear. Late-onset, sporadic Alzheimer disease (AD) is a common and lethal neurodegenerative disorder and many germline inherited variants have been found to influence the risk of developing AD. Our previous results show that a fundamentally different genetic variant, i.e., lifetime-acquired loss of chromosome Y (LOY) in blood cells, is associated with all-cause mortality and an increased risk of non-hematological tumors and that LOY could be induced by tobacco smoking. We tested here a hypothesis that men with LOY are more susceptible to AD and show that LOY is associated with AD in three independent studies of different types. In a case-control study, males with AD diagnosis had higher degree of LOY mosaicism (adjusted odds ratio = 2.80, p = 0.0184, AD events = 606). Furthermore, in two prospective studies, men with LOY at blood sampling had greater risk for incident AD diagnosis during follow-up time (hazard ratio [HR] = 6.80, 95% confidence interval [95% CI] = 2.16-21.43, AD events = 140, p = 0.0011). Thus, LOY in blood is associated with risks of both AD and cancer, suggesting a role of LOY in blood cells on disease processes in other tissues, possibly via defective immunosurveillance. As a male-specific risk factor, LOY might explain why males on average live shorter lives than females.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
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- ref (ämneskategori)
- art (ämneskategori)
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Dumanski, Jan P.
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Lambert, Jean-Ch ...
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Rasi, Chiara
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Giedraitis, Vilm ...
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Davies, Hanna
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Grenier-Boley, B ...
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Lindgren, Cecili ...
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Campion, Dominiq ...
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Dufouil, Carole
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Pasquier, Floren ...
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Amouyel, Philipp ...
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Lannfelt, Lars
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Ingelsson, Marti ...
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Kilander, Lena
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Lind, Lars
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Forsberg, Lars A ...
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