Genetic determinants of plasma lipids in Greenlanders

PURPOSE OF REVIEW Greenlanders differ from other populations in terms of traditional lifestyle and genetic architecture. This might have a great impact on lipid levels in the population and the spectrum of genetic variants associated with lipid traits. Here, we review recent advances in lipid genetics in Greenlanders and highlight the potential of moving from single lipid trait analyses to more comprehensive lipidomic profiling.

RECENT FINDINGS Genetic association studies in the Greenlandic population have identified variants, including PCSK9 (rs12117661), LDLR (rs730882082), and SI (rs781470490), associated with large effects on triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and total cholesterol (TC) levels, as well as altered risk of cardiovascular disease (CVD). These variants are common in the Greenlandic population and explain more lipid variation than variants observed in Europeans. Accordingly, European-derived polygenic scores (PGSs) underperform in Greenlanders, but including the Greenlandic variants increases the performance of lipid PGSs. Lipidomic profiling has the potential to reveal strong cardiometabolic-risk signatures.

SUMMARY The Greenlandic population harbors high-impact variants in PCSK9, LDLR, and SI, particularly affecting the levels of TG, LDL-C, and TC. Obtaining information on these variants could facilitate earlier detection and potentially prevention of CVD, and advance precision medicine for Greenlanders.