| Title: |
Age acquired skewed X chromosome inactivation is associated with adverse health outcomes in humans |
| Authors: |
Roberts, AL; Morea, A; Amar, A; Zito, A; Moustafa, JSES; Tomlinson, M; Bowyer, RCE; Zhang, X; Christiansen, C; Costeira, R; Steves, CJ; Mangino, M; Bell, JT; Wong, CCY; Vyse, TJ; Small, KS |
| Source: |
eLife , 11 , Article e78263. (2022) |
| Publisher Information: |
eLife Sciences Publications, Ltd |
| Publication Year: |
2022 |
| Collection: |
University College London: UCL Discovery |
| Description: |
Background: Ageing is a heterogenous process characterised by cellular and molecular hallmarks, including changes to haematopoietic stem cells and is a primary risk factor for chronic diseases. X chromosome inactivation (XCI) randomly transcriptionally silences either the maternal or paternal X in each cell of 46, XX females to balance the gene expression with 46, XY males. Age acquired XCI-skew describes the preferential selection of cells across a tissue resulting in an imbalance of XCI, which is particularly prevalent in blood tissues of ageing females, and yet its clinical consequences are unknown. / Methods: We assayed XCI in 1575 females from the TwinsUK population cohort using DNA extracted from whole blood. We employed prospective, cross-sectional, and intra-twin study designs to characterise the relationship of XCI-skew with molecular and cellular measures of ageing, cardiovascular disease risk, and cancer diagnosis. / Results: We demonstrate that XCI-skew is independent of traditional markers of biological ageing and is associated with a haematopoietic bias towards the myeloid lineage. Using an atherosclerotic cardiovascular disease risk score, which captures traditional risk factors, XCI-skew is associated with an increased cardiovascular disease risk both cross-sectionally and within XCI-skew discordant twin pairs. In a prospective 10 year follow-up study, XCI-skew is predictive of future cancer incidence. / Conclusions: Our study demonstrates that age acquired XCI-skew captures changes to the haema-topoietic stem cell population and has clinical potential as a unique biomarker of chronic disease risk. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://discovery.ucl.ac.uk/id/eprint/10170130/1/Age%20acquired%20skewed%20X%20chromosome%20inactivation%20is%20associated%20with%20adverse%20health%20outcomes%20in%20humans.pdf; https://discovery.ucl.ac.uk/id/eprint/10170130/ |
| Availability: |
https://discovery.ucl.ac.uk/id/eprint/10170130/1/Age%20acquired%20skewed%20X%20chromosome%20inactivation%20is%20associated%20with%20adverse%20health%20outcomes%20in%20humans.pdf; https://discovery.ucl.ac.uk/id/eprint/10170130/ |
| Rights: |
open |
| Accession Number: |
edsbas.D4E81EA |
| Database: |
BASE |