The subjective and symptomatic basis of psychiatric diagnoses—coupled with high rates of comorbidity, clinical heterogeneity, and the overwhelming complexity of the human brain—has greatly hindered a rigorous biological formulation necessary for rational therapeutic development. Despite this, among the most immutable characteristics of psychiatric disorders is that they run in families. It is now clear that nearly all psychiatric traits have a substantial heritable component that appears to contribute to most of the disease liability ( 1 Gandal M.J. Leppa V. Won H. Parikshak N.N. Geschwind D.H. The road to precision psychiatry: Translating genetics into disease mechanisms. Nat Neurosci. 2016; 19: 1397-1407 Crossref PubMed Scopus (118) Google Scholar ). There is substantial optimism that identifying the underlying genetic risk factors contributing to this heritability will provide a rigorous, quantitative foothold that can advance our understanding of disease mechanisms ( 2 Hyman S.E. Wringing biological insight from polygenic signals. Biol Psychiatry. 2021; 89: 8-10 Google Scholar ). After years of false starts, the last decade has seen tremendous gains in the identification of now hundreds of robust disease-associated genetic variants. This success can be attributed to the move from candidate gene to genome-wide studies, coupled with rigorous statistical analyses and parallel increases in study sample size owing to international collaborative efforts ( 3 Sullivan P.F. Geschwind D.H. Defining the genetic, genomic, cellular, and diagnostic architectures of psychiatric disorders. Cell. 2019; 177: 162-183 Abstract Full Text Full Text PDF PubMed Scopus (156) Google Scholar ). Based on these advances, the number of replicated, genome-wide significant disease loci are expected to rise exponentially in the coming years. As we enter the post–genome-wide association study (GWAS) era, the next substantial challenge is how to interpret such genetic risk within an individual and at a population level ( 1 Gandal M.J. Leppa V. Won H. Parikshak N.N. Geschwind D.H. The road to precision psychiatry: Translating genetics into disease mechanisms. Nat Neurosci. 2016; 19: 1397-1407 Crossref PubMed Scopus (118) Google Scholar ).