Abstract
Plasma lipidome is now increasingly recognized as a potentially important marker of chronic diseases, but the exact extent of its contribution to the interindividual phenotypic variability in family studies is unknown. Here, we used the rich data from the ongoing San Antonio Family Heart Study (SAFHS) and developed a novel statistical approach to quantify the independent and additive value of the plasma lipidome in explaining metabolic syndrome (MS) variability in Mexican American families recruited in the SAFHS. Our analytical approach included two preprocessing steps: principal components analysis of the high-resolution plasma lipidomics data and construction of a subject-subject lipidomic similarity matrix. We then used the Sequential Oligogenic Linkage Analysis Routines software to model the complex family relationships, lipidomic similarities, and other important covariates in a variance components framework. Our results suggested that even after accounting for the shared genetic influences, indicators of lipemic status (total serum cholesterol, TGs, and HDL cholesterol), and obesity, the plasma lipidome independently explained 22% of variability in the homeostatic model of assessment-insulin resistance trait and 16% to 22% variability in glucose, insulin, and waist circumference. Our results demonstrate that plasma lipidomic studies can additively contribute to an understanding of the interindividual variability in MS.
Highlights
Plasma lipidome is increasingly recognized as a potentially important marker of chronic diseases, but the exact extent of its contribution to the interindividual phenotypic variability in family studies is unknown
We used data from the ongoing San Antonio Family Heart Study (SAFHS) in Mexican Americans [27]. These data and samples provide an appropriate opportunity for the aforementioned investigation for the following reasons: i) metabolic syndrome (MS) is very common in Mexican Americans [28]; ii) the SAFHS recruited 42 large and extended pedigrees that help delineate the potential contribution of genetics to MS [29, 30]; iii) high-resolution plasma lipidomic studies have been conducted on a large number of SAFHS participants [15]; and iv) using these data, we have previously demonstrated that specific lipid species are associated with hypertension [15], central obesity [31], and type 2 diabetes [32]
We addressed the following three research questions: First, what is the degree of variability in MS-related traits that can be ascribed to the plasma lipidome in Mexican American families? Second, is this association independent of and additive to the known association of MS with clinically used measures of lipemic status like total serum cholesterol, serum TGs, and serum HDL chlolesterol (HDL-C)? Third, is the association of plasma lipidome with MS independent of obesity?
Summary
Plasma lipidome is increasingly recognized as a potentially important marker of chronic diseases, but the exact extent of its contribution to the interindividual phenotypic variability in family studies is unknown. We used data from the ongoing San Antonio Family Heart Study (SAFHS) in Mexican Americans [27] These data and samples provide an appropriate opportunity for the aforementioned investigation for the following reasons: i) MS is very common in Mexican Americans [28]; ii) the SAFHS recruited 42 large and extended pedigrees that help delineate the potential contribution of genetics to MS [29, 30]; iii) high-resolution plasma lipidomic studies have been conducted on a large number of SAFHS participants [15]; and iv) using these data, we have previously demonstrated that specific lipid species are associated with hypertension [15], central obesity [31], and type 2 diabetes [32]
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