Life course epidemiology is defined as the study of long term effects on later health or (often multi factorial, chronic) disease risk of physical or social exposures during gestation, childhood, adolescence, young adulthood and later adult life. Studying these associations raises statistical problems as risk factors act in a temporal fashion, often having both a direct effect on the early, preclinical development of disease and on the occurrence or strength of other risk factors (effect modification). Recently within the UMCG a large three-generation population-based study to multi factorial disease has started: LifeLines. The aim of this study is to investigate universal risk factors and their modifiers for multi factorial diseases. General mixed and joint biostatistical models have been developed to analyse the data collected, but these do not optimally use the three generation data and do not quantify the effects of modifiers. This research will aim at developing practical solutions to analyse data from three generation population-based studies which will be applicable both for the Groningen LifeLines project as well as for other cohort studies at the UMCG (Prevend, TRAILS, GLAS...).