Common SNPs in FTO gene are associated with obesity related anthropometric traits in an island population from the eastern Adriatic coast of Croatia

Abstract

Background: Multiple studies have provided compelling evidence that the FTO gene variants are associated with obesity measures. The objective of the study was to investigate whether FTO variants are associated with a broad range of obesity related anthropometric traits in an island population.

Methodology/principal findings: We examined genetic association between 29 FTO SNPs and a comprehensive set of anthropometric traits in 843 unrelated individuals from an island population in the eastern Adriatic coast of Croatia. The traits include 11 anthropometrics (height, weight, waist circumference, hip circumference, bicondilar upper arm width, upper arm circumference, and biceps, triceps, subscapular, suprailiac and abdominal skin-fold thicknesses) and two derived measures (BMI and WHR). Using single locus score tests, 15 common SNPs were found to be significantly associated with "body fatness" measures such as weight, BMI, hip and waist circumferences with P-values ranging from 0.0004 to 0.01. Similar but less significant associations were also observed between these markers and bicondilar upper arm width and upper arm circumference. Most of these significant findings could be explained by a mediating effect of "body fatness". However, one unique association signal between upper arm width and rs16952517 (P-value = 0.00156) could not be explained by this mediating effect. In addition, using a principle component analysis and conditional association tests adjusted for "body fatness", two novel association signals were identified between upper arm circumference and rs11075986 (P-value = 0.00211) and rs16945088 (P-value = 0.00203).

Conclusions/significance: The current study confirmed the association of common variants of FTO gene with "body fatness" measures in an isolated island population. We also observed evidence of pleiotropic effects of FTO gene on fat-free mass, such as frame size and muscle mass assessed by bicondilar upper arm width and upper arm circumference respectively and these pleiotropic effects might be influenced by variants that are different from the ones associated with "body fatness".

Figure 1. Geographical location of Hvar and the 8 villages from where the samples were collected.

Figure 2. Hierarchical clustering of the 13 anthropometric traits.

Figure 3. Distribution and pairwise LD (r ²) map of the 29 SNP markers.

Figure 4. P values of association tests.

A) Association test P values between “body fatness” measures (Wt, BMI, WC, HC) and PC1; B) Association test P values of UAW, PC2 and PC1 adjusted UAW (UAW|PC1); C) Association test P values of UAC, PC3 and PC1 adjusted UAC (UAC|PC1).