Abstract
Context. A number of studies have reported replicable associations between common genetic loci and obesity indices. One of these loci is the fat mass and obesity associated locus (FTO). We aimed to assess whether breastfeeding mediated the known association between FTO and indices of body fatness. Methods. This study includes three independent pediatric cohorts, two of Greek origin (the Gene-Diet Attica Investigation: GENDAI, n=1 138 and the “Growth, Exercise and Nutrition Epidemiological Study In preschoolers”: the GENESIS study, n=2 374) and one British (the Avon Longitudinal Study of Parents and Children:ALSPAC, n=4 325). Among other information, breastfeeding history was recorded. A DNA sample was ascertained by either blood or saliva. Genotyping for FTO variants was performed in GENDAI and ALSPAC for the rs9939609, while in GENESIS, for the rs17817449 variant. Results. In all cohorts, multivariate analysis showed that the association between FTO:rs9939609 and measures of obesity was consistent across newly presented cohorts (GENDAI: Body mass index [BMI], β=0.43, p=0.009; Waist Circumference, β=1.067, p=0.019; triceps skinfold, β=0.972, p=0.003; subscapular skinfold, β=0.593, p=0.023; GENESIS: Waist Circumference, β=0.473, p=0.008 and subscapular skinfold, β=0.227, p=0.014). Inclusion of one month of breastfeeding as an interaction term effectively removed these associations with indices of obesity (BMI, Waist-Hip-Ratio and subscapular skinfold). No evidence of such interaction was observed for the independent cohort of British children. Conclusions. Our findings indicate that in two moderately sized Greek samples, breastfeeding may exert a modifying effect on the relationship between variants at the FTO locus and indices of adiposity. These findings were not replicated in a larger British collection.
Key words::
Acknowledgements
We thank our participating children and their schools for their help and enthusiasm. Sources of Support: The collection of the GENDAI cohort was funded by Coca-Cola Hellas, whereas the genotyping was funded by NIDDK K23 DK067288, awarded to HNL. The collection of GENESIS was supported by a grant from Friesland Foods Hellas and the genotyping was funded in part by grant 17/D17566 from the Medical Research Council/Biotechnology and Biological Sciences Research Council associate program in human nutrition research. We are extremely grateful to all the families who took part in the ALSPAC study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses. The UK Medical Research Council, the Wellcome Trust and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors (George VZ Dedoussis, Mary Yannakoulia, Nicholas J Timpson, Yannis Manios, Stavroula Kanoni, Robert A. Scott, Constantina Papoutsakis, Panos Deloukas, Yannis P. Pitsiladis, George Davey-Smith, Joel N. Hirschhorn and Helen N. Lyon) and the authors will serve as guarantors for the contents of this paper.
Abbreviations
BMI: Body Mass Index; WHR: Waist-to-Hip Ratio; MAF: Minor Allele Frequency; FTO: Fat mass and obesity associated locus.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.