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Approved research

Numerical abnormalities and structural rearrangements of the Y and X chromosomes and predisposition to complex diseases

Principal Investigator: Professor Maciej Tomaszewski
Approved Research ID: 32497
Approval date: April 3rd 2018

Lay summary

Women and men share a set of 22 pairs of chromosomes called autosomes. In addition to these, men carry a Y chromosome, passed from fathers to sons as an indivisible portion of DNA. Men also carry one copy of the much larger X chromosome, while women carry two X copies. Our earlier studies showed that one of the Y chromosome?s paternally-inherited lineages (haplogroups) is associated with increased risk to coronary artery disease. We wish to examine if other types of genetic variation of the Y chromosome and multiple X chromosomes are associated with the risk of common diseases. Understanding the biological mechanisms underlying many common disorders is one of the major goals of UK Biobank. The resource was established to facilitate research into better understanding of why certain individuals are more predisposed to common disorders than others. To this end, we wish to examine whether and how different types of genetic variations of the sex chromosomes make their carriers more susceptible to common diseases. The data from this project will help to improve understanding of the role of the sex chromosomes in susceptibility to common disorders, with a potential to develop stratified approaches to their prediction and therapy. We will use genetic information provided by 813 Y-chromosome markers on the UK Biobank Axiom® Array to identify men with polysomy and known large deletions/duplications of the Y chromosome. We will also use information provided by the 21,084 X-chromosome markers to identify individuals who have X-chromosome polysomy. We will first validate the array-based genetic variations using direct DNA analysis. We will then compare carriers of these sex chromosomes mutations in relation to common non-communicable diseases (i.e. cardiovascular, respiratory, metabolic, cancer), their intermediate phenotypes and the mortality rates. We request access to all UK Biobank participants. Our interest in the Y chromosome and the effect of paternal lineages on health means we need to study all male participants. However, because we also wish to understand the effect of X-chromosome polysomy, we also need to study female participants, even though only a small proportion of these are expected to carry multiple copies of the X chromosome.