First, we systematically reviewed the literature that aimed to link risk tolerance to biological pathways (Supplementary Note). Our review covered studies based on candidate genes (i.e., specific genetic variants used as proxies for biological pathways), pharmacological manipulations, biochemical assays, genetic manipulations in rodents, as well as other research designs. Our review identified 132 articles that matched our search criteria (Supplementary Table 1). This previous work has focused on five main biological pathways: the steroid hormone cortisol, the monoamines dopamine and serotonin, and the steroid sex hormones estrogen and testosterone. Using a MAGMA31 competitive gene-set analysis, we found no evidence that SNPs within genes associated with these five pathways tend to be more associated with general risk tolerance than SNPs in other genes (Supplementary Table 15). Furthermore, none of the other bioinformatics analyses we report below point to these pathways.
