Genetic determinants of common obesity and their value in prediction.
ABSTRACT Genome-wide association studies (GWAS) have revolutionised the discovery of genes for common traits and diseases, including obesity-related traits. In less then four years time, 52 genetic loci were identified to be unequivocally associated with obesity-related traits. This vast success raised hope and expectations that genetic information would become soon an integral part of personalised medicine. However, these loci have only small effects on obesity-susceptibility and explain just a fraction of the total variance. As such, their accuracy to predict obesity is poor and not competitive with the predictive ability of traditional risk factors. Nevertheless, some of these loci are being used in commercially available personal genome tests to estimate individuals' lifetime risk of obesity. While proponents believe that personal genome profiling could have beneficial effects on behaviour, early reports do not support this hypothesis. To conclude, the most valuable contribution of GWAS-identified loci lies in their contribution to elucidating new physiological pathways that underlie obesity-susceptibility.
SourceAvailable from: Aline Meirhaeghe[Show abstract] [Hide abstract]
ABSTRACT: Background Genome-wide association studies have identified variants associated with BMI in populations of European descent. We sought to establish whether genetic variants that are robustly associated with BMI could modulate anthropometric traits and the obesity risk in an Algerian population sample, the ISOR study.The ISOR study of 787 adult subjects (aged between 30 and 64) provided a representative sample of the population living in the city of Oran (north-west of Algeria). We investigated the combined effect of 29 BMI established genetic variants using a genetic predisposition score (GPS) on anthropometric traits and obesity risk in 740 subjects.ResultsWe found that each additional risk allele in the GPS was associated with an increment in the mean [95% CI] for BMI of 0.15 [0.06 - 0.24] kg/m2 (p¿=¿0.001). Although the GPS was also associated with higher waist (p¿=¿0.02) and hip (p¿=¿0.02) circumferences, these associations were in fact driven by BMI. The GPS was also associated with an 11% higher risk of obesity (OR [95%CI]¿=¿1.11 [1.05 - 1.18], p¿=¿0.0004).Conclusions Our data showed that a GPS comprising 29 BMI established loci developed from Europeans seems to be a valid score in a North African population. Our findings contribute to a better understanding of the genetic susceptibility to obesity in Algeria.BMC Genetics 11/2014; 15(1):128. DOI:10.1186/s12863-014-0128-1 · 2.36 Impact Factor
Article: Genetic aspects of human obesity.[Show abstract] [Hide abstract]
ABSTRACT: Obesity and its related metabolic consequences represent a major public health problem. Huge changes within the environment have undoubtedly contributed to the increased prevalence of obesity but genetic factors are also critical in determining an individual's predisposition to gain weight. The last two decades have seen a huge increase in the understanding of the mechanisms controlling appetitive behavior, body composition, and energy expenditure. Many regions throughout the central nervous system play critical roles in these processes but the hypothalamus, in particular, receives and orchestrates a variety of signals to bring about coordinated changes in energy balance. Reviewing data from human genetic and model organism studies, we consider how disruptions of hypothalamic pathways evolved to maintain energy homeostasis and go on to cause obesity. We highlight ongoing technological developments which continue to lead to novel insights and discuss how this increased knowledge may lead to effective therapeutic interventions in the future.Handbook of Clinical Neurology 01/2014; 124C:93-106. DOI:10.1016/B978-0-444-59602-4.00006-X
Metabolism: clinical and experimental 10/2014; DOI:10.1016/j.metabol.2014.09.012 · 3.61 Impact Factor