Using genomic sequencing, genetic linkage, functional validation, and transcriptome analysis, we found that a Grm2 stop codon functions as a genetic determinant for alcohol preference in selectively bred alcohol preferring (P) and nonpreferring (NP) rats (Zhou et al., 2013). In contrast, genetic studies in humans to identify genes and variants underlying complex disorders and addiction have achieved only limited success, largely due to genetic heterogeneity and the limited effect size of individual loci. Animals selectively bred for alcohol and drug dependence provide potentially powerful models for the identification of genetic variants influencing addiction behaviors both because the artificial selection may collect to high frequencies variants that are rare or uncommon in the ancestral population and because of the ability to control environmental exposures and test animals under the same conditions. By exome sequencing, we uncovered a Grm2 C407* variant from 25,715 SNPs that homozygously segregates between P and NP rats. All P rats were homozygous for this stop codon in the mGluR2 receptor ligand-binding domain, whereas none of the NP rats carried this allele. The levels of Grm2 transcript in
