Identification of shared genetic risks underlying metabolic syndrome and its related traits in the Korean population

Abstract

Introduction: Observational studies have demonstrated strong correlations between metabolic syndrome (MetS) and its related traits. To gain insight into the genetic architecture and molecular mechanism of MetS, we investigated the shared genetic basis of MetS and its related traits and further tested their causal relationships.Methods: Using summary statistics from genome-wide association analyses of about 72,000 subjects from the Korean Genome and Epidemiological Study (KoGES), we conducted genome-wide multi-trait analyses to quantify the overall genetic correlation and Mendelian randomization analyses to infer the causal relationships between traits of interest.Results: Genetic correlation analyses revealed a significant correlation of MetS with its related traits, such as obesity traits (body mass index and waist circumference), lipid traits (triglyceride and high-density lipoprotein cholesterol), glycemic traits (fasting plasma glucose and hemoglobin A1C), and blood pressure (systolic and diastolic). Mendelian randomization analyses further demonstrated that the MetS-related traits showing significant overall genetic correlation with MetS could be genetically determined risk factors for MetS.Discussion: Our study suggests a shared genetic basis of MetS and its related traits and provides novel insights into the biological mechanisms underlying these complex traits. Our findings further inform public health interventions by supporting the important role of the management of metabolic risk factors such as obesity, unhealthy lipid profiles, diabetes, and high blood pressure in the prevention of MetS.