A study co-led by researchers at the National Cancer Institute of the National Institutes of Health (NIH) in the United States has identified inherited genetic variants that can predict the loss of one copy of both of a woman’s X chromosomes as she ages. This phenomenon is known as mosaic loss of the X chromosome, or mLOX.
The results of the study have been published in the journal Nature and confirm that women with mLOX have an increased risk of developing blood cancers such as leukaemia and are also more prone to infections such as pneumonia, highlighting the potential health implications of this chromosomal abnormality.
These genetic variants could play a role in promoting the multiplication of abnormal blood cells (which have only one copy of the X chromosome), which could lead to various health problems, including cancer and, specifically, myeloid and lymphoid leukemias.
Causes and consequences of X chromosome loss
To better understand the causes and effects of mLOX, the researchers analyzed circulating white blood cells from 883,574 women whose data were recorded in eight biobanks, 12% of whom had the condition. The researchers identified 56 common genetic variants, located near genes associated with autoimmune diseases and cancer susceptibility, that influenced the development of mLOX. In addition, rare variants in a gene known as FBXO10 were associated with a doubled risk of developing mLOX.
Researchers confirmed that mLOX was associated with an increased risk of leukemia and susceptibility to infections that cause pneumonia.
In women with mLOX, the researchers also identified a set of inherited genetic variants on the X chromosome that were seen more frequently on the retained X chromosome than on the lost one. These variants could be used in the future to predict which copy of the X chromosome is retained when mLOX occurs. This is important because the copy of the X chromosome with these variants could have a growth advantage that increases a woman’s risk of blood cancer.
The researchers also looked for associations of mLOX with more than 1,200 diseases and confirmed previous findings of an association with increased risk of leukemia and susceptibility to infections that cause pneumonia. They suggest that future research should focus on how mLOX interacts with other types of genetic variations and age-related changes to potentially alter disease risk.
