Principal Investigator: Professor Maciej Tomaszewski

Department: Division of Cardivascular Sciences

Institution: University of Manchester

Institution:

Lead Collaborators: 1) Professor Fadi Charchar and 2) Professor Mark Jobling

Collaborating Institutions and Addresses:

1) Federation University Australia, School of Applied & Biomedical Sciences, University Drive, Mt. Helen, Ballarat, Victoria 3350, Australia

2) University of Leicester, Department of Genetics, Adrian Building, University Road, Leicester, LE1 7RH, United Kingdom

Summary:

1a: 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).

1b: 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.

1c: 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.

1d: We intend to use information from men of white British ancestry only.

Project extension:

APPROVED 03.07.2017:
“Having developed a robust system of phylogenetic analysis of the Y chromosome based on the markers available on Axiom array we propose:
1) extending the number of diseases to a wider range of diagnoses linked either to cardiovascular system, immunity/inflammation or ageing
2) inclusion of the full spectrum of haplogroups of the Y chromosome in association analyses
3) establishing whether the associations between haplogroups of the Y chromosome and the susceptibility to disease is linked to the Y chromosome loss”

PDF File

Last updated Jul 14, 2017