Mosaic Loss of Chromosome Y in Blood Is Associated with Alzheimer Disease
2016 (English)In: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 98, no 6, 1208-1219 p.Article in journal (Refereed) PublishedText
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.
Place, publisher, year, edition, pages
2016. Vol. 98, no 6, 1208-1219 p.
IdentifiersURN: urn:nbn:se:uu:diva-299047DOI: 10.1016/j.ajhg.2016.05.014ISI: 000377286000014PubMedID: 27231129OAI: oai:DiVA.org:uu-299047DiVA: diva2:948797
FunderStiftelsen Olle Engkvist ByggmästareEU, European Research CouncilSwedish Cancer SocietySwedish Research CouncilSwedish Heart Lung FoundationTorsten Söderbergs stiftelseWellcome trust, WT098017 WT064890 WT090532