we opted to use Genomic Restricted maximum likelihood (GREML) to understand the relationship among the 11 AUD symptoms because our sample sizes precluded the use of genomewide association analysis which would have resulted in biased SNP-estimates that reflect only a small portion of the phenotypic heritability (i.e., missing heritability; (Manolio et al., 2009)). In the current analysis, we were interested in quantifying the heritability and co-heritability due to common variation. In GREML, there is less emphasis on detecting the small effects of the common variants, but instead more emphasis on aggregated effects. Our examination of alternative factorial configurations of the criteria (i.e., correlated abuse and dependence genetic factors) provides novel evidence supporting the assumption that the genetic architecture across AUD symptoms is largely shared. Indeed, as the data suggest, GWAS aimed at the factors of tolerance, loss of control and withdrawal (Kendler et al., 2011) may yield loci distinct from those identified using a unidimensional factor score or diagnosis, because of limited power to detect such specificity and also because of AUD-symptom-specific genetic variance. As such, future works should consider analyzing AUD measures in their various forms.
