To address this hypothesis, we obtained repository blood samples collected as part of a large genetics study (COGEND) previously used for genome-wide association studies628. iPSC were prepared from cryopreserved, de-identified repository lymphocyte specimens. This strategy is particularly appealing because it allows access to large numbers of genetically diverse samples large from studies with cryopreserved specimens each having a clear clinical diagnostic history. We have developed reliable and reproducible methods to convert cryopreserved primary T-cells isolated from the RUCDR Infinite Biologics™ cell repository to iPSC24, and we successfully used this approach to study effects of alcohol on NSCs41 and mutations found in Ataxia telangiectasia42. We selected donors carrying homozygous rs16966968 major or minor allele, encoding the D398 or N398 variant, respectively, of the nAChR α5 subunit. Samples also contained homozygous major alleles for several related SNPs (Supplemental Table 1), particularly rs880395, since it has been reported to have secondary effects on CHRNA5 mRNA levels37. The goal was to represent isolated genotypes in order to test the difference between the major and minor allele of rs16969968. It has been suggested that cell
