Mosaic Loss of Chromosome Y in Blood Is Associated with Alzheimer Disease [Elektronisk resurs]
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Dumanski, Jan P. (författare)
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Lambert, Jean-Charles (författare)
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Rasi, Chiara (författare)
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Giedraitis, Vilmantas (författare)
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Davies, Hanna (författare)
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Grenier-Boley, Benjamin (författare)
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Lindgren, Cecilia M. (författare)
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Campion, Dominique (författare)
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Dufouil, Carole (författare)
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Pasquier, Florence (författare)
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Amouyel, Philippe (författare)
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Lannfelt, Lars (författare)
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Ingelsson, Martin, 1965- (författare)
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Kilander, Lena (författare)
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Lind, Lars (författare)
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Forsberg, Lars A. (författare)
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Uppsala universitet Medicinska och farmaceutiska vetenskapsområdet (utgivare)
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Uppsala universitet Science for Life Laboratory, SciLifeLab (utgivare)
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Uppsala universitet Medicinska och farmaceutiska vetenskapsområdet (utgivare)
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Uppsala universitet Medicinska och farmaceutiska vetenskapsområdet (utgivare)
- Publicerad: 2016
- Engelska.
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Ingår i: American Journal of Human Genetics. - 0002-9297. ; 98:6, 1208-1219
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- 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.
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- Medical and Health Sciences (hsv)
- Basic Medicine (hsv)
- Medical Genetics (hsv)
- Medicin och hälsovetenskap (hsv)
- Medicinska grundvetenskaper (hsv)
- Medicinsk genetik (hsv)
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American Journal of Human Genetics