The predictive effect of family genetic risk scores as an indirect measure of causal effects of one disorder on another.

BACKGROUND

One potential cause of comorbidity is the direct causal effect of one disorder - A - on risk for subsequent onset of disorder B. Could genetic risk scores be utilized to test for such an effect? If disorder A causally impacts on risk for disorder B, then genetic risk for disorder A should be lower in cases of disorder A with

METHODS

In all individuals (

RESULTS

In all pairs, the impact of the FGRS for disorder B was significantly stronger in cases without

CONCLUSIONS

Our findings provide indirect evidence that the occurrence of one psychiatric or substance use disorder often has a causal effect on risk for subsequent disorders. This mechanism may substantially contribute to the widespread comorbidity among psychiatric conditions.