by 2.5 mg/dl for each copy of the protective allele, with even smaller associations with coronary artery disease, while statins typically decrease LDL by 14–70 mg/dL. This example is not unique. Similar observations of large medication effects targeting proteins in which common genetic variation is more modestly associated with disease expression, have been observed across a host of phenotypes (e.g., bone density and estrogens (Hirschhorn and Gennari, 2008)). Indeed, a recent investigation finds that drug targets with evidence of disease association through GWAS are twice as likely to be met with success (Nelson et al., 2015). These results suggest that common genetic variation linked to intermediate phenotypes (e.g., cholesterol for coronary artery disease), and also with disease risk at modest effect sizes, have the potential for great therapeutic value. Similar expectations for psychiatric disorders are not unrealistic (Breen et al., 2016, Wendland and Ehlers, 2016). GWAS may be a particularly fruitful pathway to such discovery, especially within the field of psychiatry, which has thus far struggled to identify mechanistic pathways that may be leveraged for treatment outside of happenstance [e.g., the observed mood benefits of an agent developed to treat tuberculosis that inhibited monoamine oxidase and led to the development
