Genetically Determined Height and Coronary Artery Disease

There is a well-established association between a shorter adult height and an increased risk of coronary artery disease (CAD). Shorter stature is also associated with risk factors for CAD, including high blood pressure, high levels of low-density lipoprotein (LDL) cholesterol, and diabetes. An individual-level meta-analysis showed that a decrease of SD (approximately 6.5 cm) in height was associated with a relative increase of 8% (95% confidence interval [CI], 6 to 10) in the risk of fatal or nonfatal CAD. The effect was largely unchanged after adjustment for smoking status, systolic blood pressure, history of diabetes, body-mass index, lipid markers, alcohol consumption, education level, and occupation. Therefore, the precise mechanisms linking shorter height with an increased risk of CAD remain unclear. Genetic variants that affect a trait provide a means of exploring the relationship between the trait and the disease and to identify putative mechanisms. In a genomewide association study, Lango Allen et al. identified a large number of independent genetic variants associated with adult height, which is a highly heritable trait. Large-scale genomewide association studies have also been undertaken to determine genetic variants associated with CAD5-7 and several cardiovascular risk factors. Here, we used the 180 single-nucleotide polymorphisms (SNPs) that explain about 10% of the variation in height, as identified by Lango Allen et al., and leveraged CAD-association data for the same variants for up to 193,449 persons to examine the association between genetically mediated variation in height and the risk of CAD. We also examined the association between the height-associated variants and several cardiovascular risk factors and performed bioinformatics analyses of the height-associated variants to identify other potential biologic mechanisms that could link a shorter height with an increased risk of CAD.