Integrative genetic studies of sex differences in the metabolic syndrome

The metabolic syndrome is characterized by a cluster of metabolic abnormalities, such as abdominal obesity, hyperlipidemia, insulin resistance and hypertension, predisposing individuals to cardiovascular disease and diabetes. The disease process is clearly complex, involving dynamic interactions of physiologic pathways perturbed by multiple genetic and environmental factors. Sex has also been identified as a strong risk factor for most complex genetic disorders; therefore, sex differences may have a substantial impact on the prevention, diagnosis, and treatment of disease.;By integrating a systems biology approach, we explored the influence of sex on genetic and environmental factors contributing to the metabolic syndrome. First, we determined the molecular mechanisms involved in the pathological consequences of male and female mice exposed to in utero environmental factors. Second, we investigated the molecular mechanisms of sex-biased gene expression. Furthermore, we constructed gene co-expression networks and detected sex-specific modules associated with complex traits involved in the metabolic syndrome. Lastly, utilizing a segregating mouse population, we determined the degree of preservation of genetic regulatory loci between males and females.