First, the field has paid insufficient attention to the potential causal claims surrounding EPs. A mediational model for EPs is a stronger scientific claim than a liability-index model. It is more falsifiable and hence, from a Popperian perspective, a ‘stronger’ hypothesis. However, because it contains causal claims, it is more difficult to test, especially in a nonexperimental setting. It is not an accident that models in this paper have largely used the simpler but less informative liability-index model. Walters and Owen4 would save the term EP solely for variables fitting our mediational model and would use a new term like ‘biomarker’ for risk-indicator variables. Yet it is difficult in humans to actually discriminate between liability-index and mediational models, especially when joint models (genetic factors operate directly on both EP and PD but there is also a causal path from EP to PD) are plausible alternatives. Whether an alternative term such as biomarker is warranted for genetic correlates of a PD remains a matter of debate.
