Using Genetic Risk Scores to Investigate the Development of Obesity and Nicotine Dependence

Genome-wide association studies (GWAS) are beginning to uncover the genetic roots of common chronic health conditions. However, the implications of these discoveries for public health remain unclear. Three questions are central to building a translational pipeline that links genetic discovery research with interventions to improve health: First, when in the life course do genetic risks become manifest? Second, what are the magnitudes of risks that can be predicted using genetic information? and Third, do genetic markers provide new information about risk over and above the existing technology of family health history assessment? This research addresses these questions for obesity and smoking. We use GWAS results to derive genetic risk scores (GRSs) for obesity and smoking. We validate these GRSs as measures of risk in a cohort of older adults (n=8,293). We then use the GRSs to investigate how genetic risk influences the development of obesity and smoking in a complete birth cohort (n=1,037) followed through age 38 years with >90% retention. Results reveal that (1) genetic risks manifest early in the development of obesity and smoking through processes that may be amenable to public health intervention; (2) the magnitudes of risk that can be predicted using genetic information are small; but (3) the risk information provided by genetic markers is independent of information available in a family history. These findings recommend an increased focus on childhood and adolescence in genetic discovery research and add a genetic dimension to arguments for early intervention to prevent obesity and smoking.