Traditional cardiovascular risk factors have been in the spotlight for coronary artery disease (CAD) management over the past decades. A non-modifiable risk marker is short adult stature. However, a causal role in the etiology of CAD was always questioned, since multiple confounders may also explain the inverse association between height and CAD risk. The assumption that genetic variants affecting height do so without interference of exogenous factors allows for the testing of the association between short stature, that is, genetic markers affecting height, and CAD even without measuring height. Interestingly, these studies suggest a rather multifaceted relationship between the two complex phenotypes. Indeed, investigating 180 height-associated genetic variants in 65,066 patients with CAD and 128,383 healthy controls suggests a causal relationship of short stature and CAD risk. Multiple signaling pathways affecting growth, as well as pleiotropic effects of genetic variants affecting height and lipids, seem to underlie the association between height and CAD risk.
Keywords: Mendelian randomization study; atherosclerosis; coronary artery disease; genome-wide association studies; height; myocardial infarction; short stature.