Human genetic studies have made tremendous progress in identifying loci linked to human disorders. Outside of psychiatry, these include high-risk mutations in single genes that identify specific targets for manipulation4. These include PCSK9, where individuals with ‘knockout’ mutations have lower LDL cholesterol without obvious deleterious effects, that has led to promising results in clinical trials7, loss of function mutations in SLC30A88 which reduce the risk of type 2 diabetes, and loss of function LPA mutations which reduce plasma lipoprotein(a) levels and cardiovascular disease risk.9
