Prediction and Interaction in Complex Disease Genetics: Experience in Type 1 Diabetes

Much of the public media discussion of genetics of common diseases has centered on opportunities for targeted preventive actions. At the same time, in the specialist literature, there has been extensive discussion of ‘‘interaction,’’ both between genes and between genes and environment. These two topics concern the use and interpretation of statistical models for risk of diseases with several, perhaps many, etiological risk factors, and were both the subject of lively debate some 30 to 40 years ago when such models first came into widespread use in epidemiology. Here these debates are revisited and illustrated with results from an analysis of the genetics of type 1 diabetes (T1D). Details of this analysis are provided in section 1 of Text S1.