Genetic insights into disease risk are becoming increasingly meaningful and precise with larger sample sizes, greater phenotypic dimensionality, and increased resolution of biological resources (e.g., single cell RNA sequencing of various cell types) (94). National health record studies provide leading examples, such as in a study involving 2.3 million Swedes, which found that fecundity is dramatically reduced among patients with schizophrenia, ASD, anorexia, and other disorders relative to unaffected siblings (95). This reduced fecundity indicates that negative selection rapidly purges even weakly deleterious variants from the genome (96). Leading efforts to provide easy, unified access linking genetic data, clinical records, and other national registry data such as in the UK Biobank, the BioBank Japan, the China Kadoorie Biobank, Nordic biobanks, and others will provide invaluable insights into otherwise obscured biological mechanisms and therapeutic targets. Further gains will be made as global initiatives expand the genetic diversity in psychiatric cases, aiding fine-mapping endeavors, research capacity, and the discovery of novel population-specific risk variants (97–100).
