Our discovery GWAS in both COGA-AA and COGA-EA identified genomewide significant loci. The association signal on chromosome 11 was supported by both COGA-AA and COGA-EA. Genes prioritized in this region have been supported by other GWAS. In a recent GWAS of alcohol dependence in a Thai population, the region between DBX1 and PRMT3 showed suggestive association with AD (Gelernter et al., 2018). Another study reported an association between PRMT3 and smoking (Park et al., 2015). Variants upstream of PRMT3 demonstrated suggestive association with marijuana dependence criterion count in an African-American cohort (Sherva et al., 2016). Although HTAPIP2 in this region was also prioritized by FUMA, it was not reported to be related to any neuropsychiatric diseases. Two additional genes in this region, DBX1 and SLC6A5, were prioritized by chromatin interaction mapping. DBX1 has been linked to educational achievement (Rietveld et al., 2014), which is negatively correlated with genetic liability to alcohol dependence (Walters et al., 2018), while SLC6A5 was reported to be related to schizophrenia (Deng et al., 2008), which is positively genetically correlated with AD (Walters et al., 2018). Thus, there is increasing evidence for the involvement of variants in this region to liability to problem drinking.
