Genome-wide association analyses of weight loss in a randomized controlled trial of lifestyle intervention, and combined transcriptome-wide associations in a Mediterranean population

Abstract

Although large-scale genome-wide association studies (GWAS) for obesity traits have identified more than 400 associated loci from observational studies (Figure 1), we highlight the fact that currently the number of GWAS for intentional weight change in randomized controlled trials (RCT) of lifestyle interventions is very scarce. Only a few RCT on weight loss have been carried out and recently a GWAS including 2 populations (a Canadian RCT and the Diogenes RCT) was been published (Valsesia et al, Nat Communications, 2019). Likely, at the transcriptome level, there is a scarcity of transcriptome-wide association studies (TWAS) of weight loss in RCT. Moreover, this scarcity is higher for studies including subjects from the Mediterranean countries. Therefore, our first aim was to undertake a GWAS in overweight/obese subjects from a Mediterranean population (Spain) after 1-year lifestyle intervention (including an energy restricted Mediterranean diet plus physical activity) in a RCT to identify genetic variants associated with weight loss and related outcomes. In addition, as a second aim, we carried out a TWAS in a subsample of subjects for the same intervention to identify changes in gene expression and related pathways.