We conducted genomewide association studies of SRE scores in the Collaborative Study on the Genetics of Alcoholism (COGA). First, using variance decomposition approaches for family data, we estimated the heritability of the SRE scores in the African-American and European-American COGA subsamples. The covariance between SRE-T, SRE-5, AD (defined by DSM-IV) and DSM-IV AD criterion count (used as a measurement of severity of AD) was decomposed into its genetic and environmental sources. We then performed GWAS to identify genetic variants contributing to the variation in SRE-T and SRE-5 scores. Genomewide significant loci were examined in two independent datasets and in RNA expression analysis using brain tissue from individuals with AD and controls. Finally, we derived polygenic risk scores (PRS) from these discovery GWAS and evaluated whether the polygenic effects of SRE-related variants predicted AD and DSM-IV AD criterion count in four independent AA and EA datasets.
