Mosaic Loss of Chromosome Y in Blood Is Associated with Alzheimer Disease
2016; Elsevier BV; Volume: 98; Issue: 6 Linguagem: Inglês
10.1016/j.ajhg.2016.05.014
ISSN1537-6605
AutoresJan 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,
Tópico(s)Epigenetics and DNA Methylation
ResumoMen 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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