Abstract
BackgroundMultiple 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 FindingsWe 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/SignificanceThe 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”.
Highlights
The worldwide prevalence of obesity has reached epidemic proportions in recent decades and is associated with increased risks of type 2 diabetes and cardiovascular diseases
We report here the associations of common fat mass obesity-associated (FTO) variants with these classic and other obesity related anthropometric measures including bicondilar upper arm width, upper arm circumference and five skin-fold thickness measures
The anthropometric measures we studied correlated to each other (Supplement Table S1)
Summary
The worldwide prevalence of obesity has reached epidemic proportions in recent decades and is associated with increased risks of type 2 diabetes and cardiovascular diseases. Recent genome-wide association studies (GWAS) have achieved remarkable success in unraveling the genetic basis of common diseases. Using this approach, common variants associated with adult and childhood obesity have been identified in several gene regions, including INSIG2, FTO, MC4R, BDNF, SH2B1 [10,11,12,13,14]. While the effect sizes of these variants contributing to the risk of obesity are modest, the fat mass obesity-associated (FTO) gene region has been replicated in several studies and in multiple populations [11,14,15,16,17]. 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
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