GENETIC AND LIFESTYLE RISK FACTORS FOR OBESITY AND RELATED DISEASES

Obesity is a major healthcare challenge linked to risk for type 2 diabetes (T2D) and cardiovascular disease (CVD). Recent findings have highlighted the importance of neuronal (hypothalamic) processes in determining susceptibility to obesity. Susceptibility to obesity-related disease however is largely determined by the distribution of adipose tissue in the body, with visceral obesity comprising a major risk factor. It well established that adipose depots from different parts of the body display distinct biological properties. The biological mechanisms that govern these differences are likely to be in part responsible for rendering visceral fat a major risk factor for disease.

Given this, our study has the following aims:

1. Identify key differences in the biology of subcutaneous and visceral fat. We aim to detect genetic variants that contribute to these differences through a regulatory effect and will complement findings with a parallel study in lymphoblastoid cell lines (LCLs).
2. Integrate findings with studies on regulatory variation and disease genome-wide association studies (GWAS) from collaborating groups to aid interpretation of GWAS signals and identification of functional variants.
3. Investigate the contribution of diet and lifestyle patterns to obesity and related disease risk.

Expected results include:

1. Identify key differences in gene regulation between subcutaneous fat, visceral fat and LCLs.
2. Link regulatory differences to differential risk of metabolic-related disease and evaluate whether regulatory events in blood are informative for obesity risk.
3. Link diet and lifestyle patterns to obesity indices.
4. Generate potential recommendations for clinicians and the general public to address obesity and related diseases.