Approved research

Paternal lineages of the Y chromosome and men?s health and disease

Lay summary

Present only in men, Y chromosome is passed from fathers onto sons as an indivisible portion of DNA. Our earlier studies showed that human Y chromosome may affect male?s health and susceptibility to disease, beyond fertility, most likely through pathways related to immunity and inflammation. We wish to validate a previously detected association between the Y chromosome and coronary artery disease, examine the effects of the Y chromosome on death rates from coronary artery disease and explore the potential role of the Y chromosome in other immunity/inflammation related conditions (asthma, rheumatoid arthritis, type 1 diabetes and inflammatory bowel disease). Understanding the biological mechanisms underlying many common disorders including coronary artery disease is one of the major goals of UK Biobank. In particular, the resource was established to facilitate research into better understanding of why certain individuals are more predisposed to common disorders than the others. To this end, we wish to examine whether/how common types (lineages) of the Y chromosome increase the risk of coronary artery disease and immunity/inflammation related disorders in some men more than in others. The data from this project will help to improve understanding of the role of the human Y chromosome in susceptibility to common disorders with a potential to develop stratified approaches to their prediction and therapy. Using genetic information from 807 Y chromosome markers on the UK Biobank Axiom® Array we will track each available Y chromosome into one of its paternal lineages (haplogroups). We will then compare individual lineages (i.e. haplogroup I) of the Y chromosome against the others in relation to coronary artery disease as well as inflammation-immunity related disorders (asthma, rheumatoid arthritis, type 1 diabetes and inflammatory bowel disease). This will be followed by studies of available clinical and biochemical parameters to examine whether they may explain the observed associations between the Y chromosome and immunity/inflammation related disorders. We intend to use information from men of white British ancestry only.