While there are a handful of replicated genetic associations with OUD, these variants do not account for the majority of the heritability observed for the disorder. Candidate gene studies also suffer from an inherent bias problem, since they only analyze genes with known or suspected connections to the phenotype of interest. Unbiased approaches like GWAS are essential for identifying truly novel associations and the current published GWAS have indeed succeeded in providing new genes of interest. However, these types of analyses are hampered by relevant small sample sizes, in conjunction with significant multiple testing correction. Results from GWAS of other psychiatric disorders (e.g. schizophrenia, alcoholism, etc.) have indicated high levels of polygenicity, with many relevant variants carrying small effect sizes. The statistical power to identify these variants requires large cohorts that are not currently available in the OUD field. Maximizing the potential of GWAS in OUD research will necessitate organized sample collection and meta-analyses of existing data sets. An additional lesson from other disorders is the “missing heritability” problem in which even appropriately powered GWAS are unable to explain all
