| Title: | Predictors of mosaic chromosome Y loss and associations with mortality in the UK Biobank |
| Journal: | Scientific Reports |
| Published: | 17 Aug 2018 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/30120341/ |
| DOI: | https://doi.org/10.1038/s41598-018-30759-1 |
| URL: | https://www.nature.com/articles/s41598-018-30759-1.pdf |
| Citations: | 119 (42 in last 2 years) as of 8 Aug 2024 |
Publication 2728
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
Mosaic loss of the Y chromosome (mLOY) is the most commonly reported large structural somatic event. Previous studies have indicated age and cigarette smoking increase the risk of mLOY, but the relationship of other exposures with mLOY and mLOY with disease has not been adequately investigated. We characterized mLOY in a large cohort of 223,338 men from the UK Biobank by scanning for deviations in genotyping array median log2 intensity ratios (mLRR) of the Y chromosome using a standard algorithm. A total of 3,789 (1.7%) men showed evidence for mLOY (mLRR < −0.15). In multivariable-adjusted logistic regression models, we found that mLOY increases exponentially with age (overall P-value < 4.9 × 10−324; p-value for the quadratic term = 2.1 × 10−7), and observed a strong association with current smoking (P-value = 7.8 × 10−184). We observed less mLOY in men of African ancestry (0.4%) compared to men of European ancestry (1.8%, P-value = 0.003). Although mLOY was not associated with prevalent cancer (P-value = 0.61), associations were observed for diabetes (P-value = 0.003) and cardiovascular disease (P-value = 0.01). Using Cox proportional hazards regression models, mLOY was associated with all-cause mortality among men with a high proportion of cells affected (mLRR < −0.40; HR = 1.35, 95% CI = 1.08-1.70, P-value = 0.009). In conclusion, mLOY was associated with several health-related factors as well as with all-cause mortality. Further functional studies are warranted to understand how and in what way mLOY could influence adult male health.</p>
7 Authors
- Erikka Loftfield
- Weiyin Zhou
- Barry I. Graubard
- Meredith Yeager
- Stephen J. Chanock
- Neal D. Freedman
- Mitchell J. Machiela
1 Application
| Application ID | Title |
|---|---|
| 21552 | Detection of large-scale copy-number and copy-neutral mosaic alterations in circulating leukocyte DNA of UK Biobank cancer cases and cancer-free controls |
Enabling scientific discoveries that improve human health