A second, and perhaps more perplexing outcome of GWAS is the relative lack of findings that are biologically plausible. This has led investigators to question the content of current GWAS arrays which, despite their high density, can provide inadequate coverage of certain genomic regions, owing to fewer SNPs and absence of adequate linkage disequilibrium required to impute such variants. The ADH1B polymorphism, rs1229984, serves as an example: this functional variant is neither included on commercial GWAS arrays nor reliably imputed owing to its low allele frequency in non-Asian populations. However, by genotyping it in multiple large samples, Bierut et al.101 recently revealed a genomewide significant association finding for rs1229984 with alcohol dependence.
