Systems genetics analysis of body weight and energy metabolism traits in Drosophila melanogaster

We found significant genetically based variation in all traits. Using a genome-wide association screen for single feature polymorphisms and quantitative trait transcripts, we identified 337, 211, 237, 553, and 152 novel candidate genes associated with body weight, glycogen content, triacylglycerol storage, glycerol levels, and metabolic rate, respectively. Weighted gene co-expression analyses grouped transcripts associated with each trait in significant modules of co-expressed genes and we interpreted these modules in terms of their gene enrichment based on Gene Ontology analysis. Comparison of gene co-expression modules for traits in this study with previously determined modules for life-history traits identified significant modular pleiotropy between glycogen content, body weight, competitive fitness, and starvation resistance.Combining a large phenotypic dataset with information on variation in genome wide transcriptional profiles has provided insight into the complex genetic architecture underlying natural variation in traits that have been associated with obesity. Our findings suggest that understanding the maintenance of genetic variation in metabolic traits in natural populations may require that we understand more fully the degree to which these traits are genetically correlated with other traits, especially those directly affecting fitness.Obesity is a condition characterized by an excess of adipose tissue that adversely affects human health [1]. The clinical problem of excessive adipose tissue resides in its strong association with a number of chronic diseases, such as insulin resistance, type 2 diabetes mellitus (T2DM), coronary artery disease and stroke [1]. In 2003-2004, 32.2% of the adults in the United States were obese [2]. This estimate represents a significant increase in obesity prevalence over the past 20 years, and similar trends are being observed worldwide [3]. As the rise in the incidence of obesity and related health problems continues, ther