Abstract

BackgroundDifferential plasma concentrations of circulating lipid species are associated with pathogenesis of type 2 diabetes (T2D). Whether the wide inter-individual variability in the plasma lipidome contributes to the genetic basis of T2D is unknown. Here, we investigated the potential overlap in the genetic basis of the plasma lipidome and T2D-related traits.ResultsWe used plasma lipidomic data (1202 pedigreed individuals, 319 lipid species representing 23 lipid classes) from San Antonio Family Heart Study in Mexican Americans. Bivariate trait analyses were used to estimate the genetic and environmental correlation of all lipid species with three T2D-related traits: risk of T2D, presence of prediabetes and homeostatic model of assessment – insulin resistance. We found that 44 lipid species were significantly genetically correlated with one or more of the three T2D-related traits. Majority of these lipid species belonged to the diacylglycerol (DAG, 17 species) and triacylglycerol (TAG, 17 species) classes. Six lipid species (all belonging to the triacylglycerol class and containing palmitate at the first position) were significantly genetically correlated with all the T2D-related traits.ConclusionsOur results imply that: a) not all plasma lipid species are genetically informative for T2D pathogenesis; b) the DAG and TAG lipid classes partially share genetic basis of T2D; and c) 1-palmitate containing TAGs may provide additional insights into the genetic basis of T2D.

Highlights

  • Differential plasma concentrations of circulating lipid species are associated with pathogenesis of type 2 diabetes (T2D)

  • T2D-related traits We studied three traits related to T2D: risk of T2D, presence of prediabetes and homeostatic model of assessment – insulin resistance (HOMA-IR)

  • Study participants This study included a total of 1202 individuals of Mexican American descent representing 42 extended families

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Summary

Introduction

Differential plasma concentrations of circulating lipid species are associated with pathogenesis of type 2 diabetes (T2D). We investigated the potential overlap in the genetic basis of the plasma lipidome and T2D-related traits. There is a strong genetic basis to the risk of developing type 2 diabetes (T2D) with heritability estimates approximating 60% [1, 2]. In the continued quest for early identification of T2D, it is important to find biomarkers that, at least partly, explain the genetic basis of T2D pathogenesis. Concentrations of specific plasma lipid species are considered to be potential biomarkers of type 2 diabetes (T2D) because subtle changes in the plasma. San Antonio Family Heart Study (SAFHS) – to investigate the shared genetic basis of plasma lipid species concentrations and three phenotypic traits related to T2D in the high risk population of Mexican Americans

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