COGA's family‐based design was initially used for linkage studies, but more recently has been used in genome‐wide association studies and large‐scale GWAS meta‐analyses to further identify loci and genes that contribute to AUD and other disorders. The evolution of analytic approaches in COGA reflects the field's changing understanding of the genetic architecture of AUD and psychiatric disorders more broadly. What began with early expectations about genes of large effect gave way to our contemporary understanding that many genes and genetic variants of individually small effects are involved. As a result, gene identification efforts for AUD have progressed but remain difficult owing to the extremely large number of cases needed to detect replicable genome‐wide significant loci, 174 and no single sample on its own would be adequately powered. Furthermore, while many researchers initially expected common genetic risk variants to be found in the coding regions of genes, over a decade of GWAS research has shown that the majority of common genetic variants associated with AUD and other complex phenotypes are found within non‐coding regions and exert their effects via regulatory functions.
