Fig. 3: Four possible causal explanations for the schizophrenia-PRS vs tea drinking association.

Red arrows reflect causal paths and grey dotted lines depict confounded associations induced by the causal relationships. schizophrenia ‘risk alleles’ refer to those included in the PRS, thus comprising genuine schizophrenia risk alleles (/risk haplotypes) and those with no effect on schizophrenia. a Some fraction of schizophrenia risk alleles are addiction risk alleles, which influence addiction to multiple substances. The causal relationship between cannabis and schizophrenia assumed here induces the association between schizophrenia-PRS and tea consumption, confounded-by-function (addiction here, used for illustration only); b schizophrenia risk allele frequencies vary with location (due to genetic drift, etc.) and so too do environmental factors influencing tea consumption and schizophrenia risk, inducing correlations between all three; c schizophrenia risk alleles increase risk for schizophrenia. Schizophrenia increases tea consumption; d schizophrenia risk alleles increase tea consumption. Tea consumption increases risk for schizophrenia.