uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Mosaic Loss of Chromosome Y in Blood Is Associated with Alzheimer Disease
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
Univ Lille, INSERM, CHU Lille, Pasteur Lille,U1167,RID AGE Risk Factors & Mol De, F-59000 Lille, France..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
Show others and affiliations
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) Published
Resource type
Text
Abstract [en]

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.
National Category
Medical Genetics
Identifiers
URN: urn:nbn:se:uu:diva-299047DOI: 10.1016/j.ajhg.2016.05.014ISI: 000377286000014PubMedID: 27231129OAI: oai:DiVA.org:uu-299047DiVA: diva2:948797
Funder
Stiftelsen Olle Engkvist ByggmästareEU, European Research CouncilSwedish Cancer SocietySwedish Research CouncilSwedish Heart Lung FoundationTorsten Söderbergs stiftelseWellcome trust, WT098017 WT064890 WT090532
Available from: 2016-07-13 Created: 2016-07-13 Last updated: 2017-11-28Bibliographically approved

Open Access in DiVA

fulltext(1026 kB)291 downloads
File information
File name FULLTEXT01.pdfFile size 1026 kBChecksum SHA-512
c45bfde320ece13e4393834448b6bebc8ab49ab73039bd568a8cc86b44c7c151346a2073cb29722790eb211d2eda0547d8f1bbd09df1b563488d5d77ef266ab1
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Authority records BETA

Dumanski, Jan P.Rasi, ChiaraGiedraitis, VilmantasDavies, HannaLannfelt, LarsIngelsson, MartinKilander, LenaLind, LarsForsberg, Lars A.

Search in DiVA

By author/editor
Dumanski, Jan P.Rasi, ChiaraGiedraitis, VilmantasDavies, HannaLannfelt, LarsIngelsson, MartinKilander, LenaLind, LarsForsberg, Lars A.
By organisation
Medicinsk genetik och genomikScience for Life Laboratory, SciLifeLabGeriatricsCardiovascular epidemiology
In the same journal
American Journal of Human Genetics
Medical Genetics

Search outside of DiVA

GoogleGoogle Scholar
Total: 291 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 831 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf