In depression, childhood maltreatment is an important risk factor for later diagnosis with depression. A meta-analysis of 6000 individuals confirmed strong effects for both PRS and childhood maltreatment contributing to the risk of depression but showed no evidence of an interaction [62]. In cardiovascular disease, an extensive study of lifestyle effects (diet, exercise, BMI, smoking) with polygenic risk scores showed strong effects from both sources, but no evidence of an interaction [63]. Similarly, a recent cohort study of UK Biobank participants aged > 60 without cognitive impairment, followed up for 8 years, both genetic risk and lifestyle factors predicted incidence of dementia, but no interaction was found [64]. Even though this paucity of confirmed interactions in large samples is not helpful in identifying individuals at very high risk, testing and disproving interactions are essential for correct joint modelling of genes and environment for risk prediction [65].
