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New insights into inheritance of coronary artery disease in men - the role of the Y sex chromosome


Coronary artery disease (CAD) is the leading cause of death in westernized populations.1 There are both a sexual dimorphism and geographical differences in prevalence of CAD - men are more commonly affected than women and Northern Europeans more than Southern Europeans.2, 3 We explored the role of the Y chromosome in CAD in the context of this geographical and sexual inequity. Here we show that in Europeans, the genetic legacy of Paleolithic hunter-gatherers - haplogroup I of the male specific region of the Y chromosome (MSY) is associated with increased risk of CAD. We found that carriers of the haplogroup I had an approximately 50% higher risk of CAD than men with other lineages of the Y chromosome. This association was independent of traditional cardiovascular risk factors and mediated through a modulating effect on the immune system. Since the Y chromosome is present only in males and haplogroup I is generally more common in the north than in the south of Western Europe our genetic findings may explain some of the ?male disadvantage? and ?geographical paradox? in susceptibility to CAD in Europe.

Type Journal
Authors Charchar, F.J.; Bloomer, L.D.S.; Barnes, T.A.; Cowley, M.J.; Nelson, C.P.; Wang, Y.; Denniff, M.; Debiec, R.; Christofidou, P.; Nankervis, S.; Dominiczak, A.F.; Bani-Mustafa, A.; Balmforth, A.; Hall, A.S.; Cambien, F.; Deloukas, P.; Hengstenberg, C.; Ouwehand, W.; Schunkert, H.; Packard, C.; Ford, I.; Goodall, A.H.; Jobling, M.A.; Samani, N.J.; Tomaszewski, M.
Publisher Name LANCET
Published Date 2012-03-10
Published Volume 379
Published Issue 9819
Published Pages 915-22
Status Published in-print
DOI 10.1016/S0140-6736(11)61453-0
URL link to publisher's version
OpenAccess link to author's accepted manuscript version