Abstract:

Cardiometabolic diseases including type 2 diabetes (T2D), cardiovascular disease (CVD), and obesity pose a growing global health problem, and a decay in the public metabolic health in Greenland is associated with westernization of diet and lifestyle. The genetic architecture of the modern Greenlandic population is shaped by its demographic history, geographic isolation in an Arctic
climate, and small population size, resulting in strong genetic drift and a high frequency of highimpact gene variants. Although genetic variants with high impact on metabolic health have already
been described, the genetic regulation of the plasma lipidome and its link to cardiometabolic diseases is poorly understood.

Using a state-of-the-art high-throughput mass spectrometry-based lipidomics, we aim to integrate plasma lipidomics data and genetic data from 2,539 Greenlandic individuals to better understand the link between lipid species and metabolic health. A study visit to Swedish University of Agricultural Sciences for collaboration will provide this project with nuclear magnetic resonance lipidomics
analysis, contributing with quantitative and qualitative knowledge of the study population and the potential identification of novel compounds. With genome-wide association studies, mapping of lipid quantitative trait loci (lQTLs), and colocalization analyses, we will examine the cross-sectional associations between lipid profiles, registry-based data on cardiometabolic outcomes, and genetic data to identify prognostic biomarkers and investigate biological pathways related to T2D, CVD, and
obesity. We hypothesize to see changes in the plasma lipidome in genetic loci linked to cardiometabolic disorders due to genetic drift of the Greenlandic population accompanied by westernized diet and lifestyle.

This project could offer novel insight into genetic etiology of cardiometabolic diseases to improve our understanding of molecular disease mechanisms and reveal novel targets for disease treatment and prevention in a broader perspective. The discovery of novel high-impact genetic variations associated with altered lipid profiles can contribute to understanding of metabolic health in Greenland and highlights the implications this research has for genetic precision medicine