Lipoprotein subclass profiling reveals pleiotropy in the genetic variants of lipid risk factors for coronary heart disease: A note on mendelian randomization studies

摘要

Mendelian randomization is increasingly used to infer causality in observational epidemiology (1). Confounding factors are then minimized through the random assignment of genetic predisposition. In recent extensive Mendelian randomization studies, remnant cholesterol (remnant-C) has been advanced as a causative risk factor for ischemic heart disease, independently of high-density lipoprotein (HDL) cholesterol (2,3). Remnant-C is understood as the cholesterol carried in the triglyceride-rich very-low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL) particles together with chylomicrons in the nonfasting state. It is well established that small VLDL and IDL particles (i.e., those with the highest content of cholesterol in the remnant particle category) can penetrate the arterial wall and become retained in the intima. Thus, a causal role of remnant-C is physiologically plausible. However, implying causality by using Mendelian randomization is, in many cases, not appropriate (1). Genes that regulate lipoprotein metabolism are rarely specific for 1 lipid measure or a single lipoprotein (4).