Journal article

Human Y Chromosome Exerts Pleiotropic Effects on Susceptibility to Atherosclerosis

James M Eales, Akhlaq A Maan, Xiaoguang Xu, Tom Michoel, Pille Hallast, Chiara Batini, Daniel Zadik, Priscilla R Prestes, Elsa Molina, Matthew Denniff, Juliane Schroeder, Johan LM Bjorkegren, John Thompson, Pasquale Maffia, Tomasz J Guzik, Bernard Keavney, Mark A Jobling, Nilesh J Samani, Fadi J Charchar, Maciej Tomaszewski

Arteriosclerosis, Thrombosis and Vascular Biology | LIPPINCOTT WILLIAMS & WILKINS | Published : 2019

Abstract

OBJECTIVE: The male-specific region of the Y chromosome (MSY) remains one of the most unexplored regions of the genome. We sought to examine how the genetic variants of the MSY influence male susceptibility to coronary artery disease (CAD) and atherosclerosis. Approach and Results: Analysis of 129 133 men from UK Biobank revealed that only one of 7 common MSY haplogroups (haplogroup I1) was associated with CAD-carriers of haplogroup I1 had ≈11% increase in risk of CAD when compared with all other haplogroups combined (odds ratio, 1.11; 95% CI, 1.04-1.18; P=6.8×10-4). Targeted MSY sequencing uncovered 235 variants exclusive to this haplogroup. The haplogroup I1-specific variants showed 2.45- ..

View full abstract

University of Melbourne Researchers

Grants

Awarded by British Heart Foundation


Awarded by National Institutes of Health R01 grant


Awarded by Estonian Research Council


Awarded by European Research Council


Awarded by Wellcome Trust


Awarded by National Health and Medical Research Council of Australia


Awarded by NATIONAL HEART, LUNG, AND BLOOD INSTITUTE


Funding Acknowledgements

The work described herein was supported by British Heart Foundation grants PG/16/49/32176 (to M. Tomaszewski), PG/12/9/29376 (to M. Tomaszewski), and RE/13/5/30177 (to T.J. Guzik and P. Maffia); National Institutes of Health R01 grant HL125863 (to J.L.M. Bjorkegren); Estonian Research Council grant PUT1036 (to P. Hallast); and European Research Council grant 726318 (to T.J. Guzik). C. Batini, P. Hallast, D. Zadik, and M.A. Jobling were supported by a Wellcome Trust Senior Fellowship grant to M.A. Jobling (087576). F.J. Charchar is supported by a National Health and Medical Research Council of Australia grant (APP 1123472).