Format

Send to

Choose Destination
Am J Hum Genet. 2016 Jun 2;98(6):1208-1219. doi: 10.1016/j.ajhg.2016.05.014. Epub 2016 May 23.

Mosaic Loss of Chromosome Y in Blood Is Associated with Alzheimer Disease.

Author information

1
Department of Immunology, Genetics, and Pathology, Uppsala University, 75108 Uppsala, Sweden; Science for Life Laboratory, Uppsala University, 75123 Uppsala, Sweden. Electronic address: jan.dumanski@igp.uu.se.
2
University Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1167 - RID-AGE - Risk Factors and Molecular Determinants of Aging-Related Diseases, 59000 Lille, France.
3
Department of Immunology, Genetics, and Pathology, Uppsala University, 75108 Uppsala, Sweden; Science for Life Laboratory, Uppsala University, 75123 Uppsala, Sweden.
4
Department of Public Health and Caring Sciences, Uppsala University, 75185 Uppsala, Sweden.
5
Wellcome Trust Centre for Human Genetics, University of Oxford, OX3 7BN Oxford, UK; Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA.
6
CNR-MAJ, Inserm, U1079, Rouen University Hospital, Rouen 76031 France.
7
Inserm, U708, Victor Segalen University, Bordeaux 33076, France.
8
Université de Lille, CNR-MAJ, Inserm 1171, Distalz, Lille 59000, France; CHU, Lille 59000, France.
9
Department of Medical Sciences, Uppsala University, 75185 Uppsala, Sweden.
10
Department of Immunology, Genetics, and Pathology, Uppsala University, 75108 Uppsala, Sweden; Science for Life Laboratory, Uppsala University, 75123 Uppsala, Sweden. Electronic address: lars.forsberg@igp.uu.se.

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.

PMID:
27231129
PMCID:
PMC4908225
DOI:
10.1016/j.ajhg.2016.05.014
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center