Approved research

Loss of the Y-chromosome in cardiovascular disease

Lay summary

Recently the Y-chromosome was found to have functions besides sex determination: it contains genes that regulate gene expression on other chromosomes. This makes the Y-chromosome interesting in disease biology, especially in diseases with different prevalence and incidence between the sexes. Loss of the Y-chromosome (LOY) in blood cells was found to be associated with aging and mortality. In mice, the expression of genes in immune cells was regulated by LOY. Since immune response is important in the development of cardiovascular disease, we aim to investigate if LOY is associated with cardiovascular risk factors and disease in men. Investigating the (immune-regulatory role) of the Y-chromosome in the pathophysiology of cardiovascular disease could lead to new ways to early identify patients at risk, it could act as a biomarker for disease or even point towards genes as potential druggable targets. Loss of the Y chromosome can be determined by raw data from the Y-chromosome from the genotyping chips (they have probes that emit a color, so less color means less signal and all signals of probes from the Y chromosome together give a median signal for the whole Y chromosome, less signal means more loss of Y). This ?intensity data? can then be correlated to different phenotypes. We aim to include all genotyped participants (150,000 and later 500,000). We are interested in the association between LOY, cardiovascular risk factors (i.e. age, smoking, cholesterol, blood pressure, BMI, diabetes) and incidence/prevalence of cardiovascular disease (acquired via HES data). In addition, immunological parameters (e.g. leukocyte differentiation) are of interest when present.