Genetics of cardiovascular disease: Importance of sex and ethnicity

Sex differences in incidence and prevalence of and morbidity and mortality from cardiovascular disease are well documented. However, many studies examining the genetic basis for cardiovascular disease fail to consider sex as a variable in the study design, in part, because there is an inherent difficulty in studying the contribution of the sex chromosomes in women due to X chromosome inactivation. This paper will provide general background on the X and Y chromosomes (including gene content, the pseudoautosomal regions, and X chromosome inactivation), discuss how sex chromosomes have been ignored in Genome-wide Association Studies (GWAS) of cardiovascular diseases, and discuss genetics influencing development of cardiovascular risk factors and atherosclerosis with particular attention to carotid intima-medial thickness, and coronary arterial calcification based on sex-specific studies. In addition, a brief discussion of how ethnicity and hormonal status act as confounding variables in sex-based analysis will be considered along with methods for statistical analysis to account for sex in cardiovascular disease.