In summary, the rich collection of genotypic and phenotypic data that COGA has generated since its inception, together with the large repository of lymphoid cells and the myriad of functional approaches that are being applied in this multimodal project (Figure 1), make COGA uniquely positioned to unravel the genetic and molecular underpinnings underlying the risk for AUD (also see 1. Overview, in this issue). Our study of postmortem brain tissues has highlighted differences between individuals with and without a history of alcohol dependence, including pathways related to inflammation. The HTRAs have identified functional SNPs within loci associated with alcohol dependence. Specific SNPs identified by COGA or by external investigators, both coding and noncoding, have been modeled using iPSC‐derived neurons from COGA participants for functional characterization. SNPs in OPRM1 and KCNJ6 impact the physiology of inhibitory (OPRM1) and excitatory (KCNJ6) neurons, respectively, highlighting a role for these neurons in AUD. In the future, AUD‐associated variants identified by COGA will be modeled in iPSC‐derived neurons using methods to selectively manipulate the expression of the gene of interest in a controlled genetic environment.
