Inheritance of coronary artery disease in men/Authors' reply

In fruit flies, the Y chromosome is a major contributor to epigenetic variation, where the expression of thousands of genes, a disproportionate number of which are immune response genes, are differentially regulated by natural polymorphic variation in tracts of heterochromatin.2,3 In mice, natural variation in the Y chromosome contributes to susceptibility to two sexually dimorphic autoimmune diseases-coxsackievirus-B3-induced myocarditis and experimental allergic encephalomyelitis, the animal model of multiple sclerosis.4,5 As in fruit flies, the Y chromosome in mammals is composed mainly of heterochromatin and contains only a limited number of functional genes. [...]proteincoding genes might not underlie these observed phenotypes, a notion that supports an evolutionarily conserved role for heterochromatin-regulated autosomal gene expression by the Y chromosome in mammals.\n1 Furthermore, introduction of both LDL cholesterol and pravastatin-based treatment as independent variables into the multiple regression model had no effect on the association between haplogroup I and CAD in this cohort (supplementary table 2).1 In this context, autosomal single-nucleotide polymorphisms (SNPs) linked to the response to statins do not seem to be likely mediators of the association between haplogroup I of the Y chromosome and CAD. [...]associations between ABO locus on chromosome 9 and CAD have been reported in genome-wide association studies.2 However, our non-metric multidimensional scaling of autosomal SNPs from previous genome-wide association studies gives us no reason to believe that there was a systematic difference in the distribution of any autosomal SNPs between carriers of haplogroup I and all other lineages (supplementary figure 1).1 Additionally, the genotype distribution of rs579459 (an ABO locus SNP associated with CAD in previous genome-wide association studies3) was similar between men with haplogroup I and other lineages of the Y chromosome in our analysis (supplementary table 4).1 Laure Case and colleagues provide an important evolutionary perspective to our findings.