Mosaic Loss of Chromosome Y in Blood Is Associated with Alzheimer Disease.
Authors | |
Abstract | 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. |
Year of Publication | 2016
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Journal | Am J Hum Genet
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Volume | 98
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Issue | 6
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Pages | 1208-19
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Date Published | 2016 Jun 02
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ISSN | 1537-6605
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URL | |
DOI | 10.1016/j.ajhg.2016.05.014
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PubMed ID | 27231129
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PubMed Central ID | PMC4908225
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Links | |
Grant list | 679744 / European Research Council / International
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