Genetically informed methods provide a powerful tool to unpack comorbidity and co-occurrence. However, even elegant methods such as the discordant twin design have their caveats. Recently, O’Brien and colleagues (91) concluded that the origins of twin discordance (for early onset cannabis use) are as pertinent as the sequelae of this discordance (e.g. other illicit drug use or low academic achievement). They advocate for a case-crossover (person-as-own-control) as an attractive alternative, however note the limitation of unmeasured covariates (92).
