Variations in many genes contribute to the risk for complex, heterogeneous disorders such as AD/AUD and traits related to them, and most have only a small effect (Edenberg and Foroud, 2013) (Gelernter et al., 2014) (Walters et al., 2018). More than 90% of the variants identified by GWAS lie in intergenic regions and do not affect the protein sequence (Hindorff et al., 2009, Maurano et al., 2012). Thus, most presumably act by altering gene expression. There are many variants within the linkage disequilibrium block that defines each locus, and the variants associated with a trait might not themselves be the functional variants. Therefore, to identify functional variants within the associated regions, highly sensitive and reliable high-throughput assays are needed.
