Genetic determinants of obesity-related lipid traits

Abstract

In our ongoing effort to identify genes influencing the biological pathways that underlie the metabolic disturbances associated with obesity, we performed genome-wide scanning in 2,209 individuals distributed over 507 Caucasian families to localize quantitative trait loci (QTLs), which affect variation of plasma lipids. Pedigree-based analysis using a quantitative trait variance component linkage method that localized a QTL on chromosome 7q35-q36, which linked to variation in levels of plasma triglyceride [TG, logarithm of odds (LOD) score = 3.7] and was suggestive of linkage to LDL-cholesterol (LDL-C, LOD = 2.2). Covariates of the TG linkage included waist circumference, fasting insulin, and insulin:glucose, but not body mass index or hip circumference. Plasma HDL-cholesterol (HDL-C) levels were suggestively linked to a second QTL on chromosome 12p12.3 (LOD = 2.6). Five other QTLs with lower LOD scores were identified for plasma levels of LDL-C, HDL-C, and total cholesterol. These newly identified loci likely harbor genetic elements that influence traits underlying lipid adversities associated with obesity.

Fig. 1

Multipoint linkage map and logarithm of odds (LOD) scores for triglyceride (blue) and LDL-cholesterol (red) on chromosome 7. The multipoint linkage results for the lipid parameters determined were adjusted for the standard set of covariates described in Methods (variance components linkage analysis).

Fig. 2

Multipoint linkage map and LOD scores for HDL-cholesterol on chromosome 12. The multipoint linkage results for the lipid parameters determined were adjusted for the standard set of covariates described in Methods.