Y chromosome mosaicism is associated with age-related macular degeneration

on behalf of the International Age-related Macular Degeneration Genomics Consortium (IAMDGC)

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Age-related macular degeneration (AMD) is the leading cause of blindness in industrialised countries, and thereby a major individual but also a socio-economic burden. Y chromosome loss in nucleated blood cells has been implicated in age-related diseases such as Alzheimer disease and was shown to be caused by increasing age, smoking and genetic factors. Mosaic loss of Y chromosome (mLOY) in peripheral blood was estimated from normalised dosages of genotyping chip data covering the male-specific region of the Y chromosome. After quality control, we assessed the association of mLOY on AMD risk in 5772 male cases and 6732 male controls. In controls the prevalence of mLOY increased significantly with age, which is consistent with previous reports. Importantly, mLOY was associated with late-stage AMD with genome-wide significance (OR: 1.332 [95% CI: 1.206; 1.472], P = 1.60e-08), independent of age, the AMD genetic risk score and the first two principle components of ancestry. Additionally conditioning on smoking behaviour had no influence on the observed association strength. mLOY was strongest associated in individuals aged between 65 and 75 years. Taken together, mLOY is significantly associated with risk for AMD, independent of known and potential confounding factors.

Original languageEnglish
Pages (from-to)36-41
Number of pages6
JournalEuropean Journal of Human Genetics
Early online date29 Aug 2018
Publication statusPublished - Jan 2019

Bibliographical note

The authors thank Sudha K. Iyengar, Rob Igo and Alberto H. Santana (Case Western Reserve University, Cleveland, Ohio, USA) as well as the IAMDGC (http://eaglep.case.edu/iamdgc_web/) for providing the raw probe intensities. We are also grateful to valuable comments to the manuscript from Michael Gorin (Jules Stein Eye Institute, Los Angeles, CA, USA). The list of consortium members reflects the author list of the previous publication by Fritsche et al. 2016 [9], which is listed in the Supplement.

The work was funded, in parts by a grant from the German Research Foundation (GR 5065/1-1 to FG) and institutional funds of the Institute of Human Genetics, University of Regensburg (TG77 to BHFW). Genotyping was conducted as part of the IAMDGC exome-chip project supported by CIDR (contract number HHSN268201200008I) and funded by EY022310 (to Jonathan L. Haines, Case Western Reserve University, Cleveland) and 1 × 01HG006934-01 (to Gonçalo R. Abecasis, University of Michigan, Department of Biostatistics). The funding bodies had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.


  • Genome-wide association studies
  • predictive markers


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