Genome-wide association study of behavioral, physiological and gene expression traits in commercially available outbred CFW mice

Although mice are the most widely used model organism, genetic studies have suffered from limited mapping resolution due to extensive linkage disequilibrium (LD) that is characteristic of crosses among inbred strains. Carworth Farms White (CFW) mice are a commercially available outbred mouse population that exhibit rapid LD decay compared to other available mouse populations. We performed a genome-wide association study (GWAS) of behavioral, physiological and gene expression phenotypes using 1,200 male CFW mice. We used genotyping-by-sequencing (GBS) to obtain genotypes at 92,734 single nucleotide polymorphisms (SNPs). We also measured gene expression using RNA-Sequencing in three brain regions. Our study identified numerous behavioral, physiological and expression quantitative trait loci (QTLs). We integrated the behavioral QTL and eQTL results to implicate specific genes, including Azi2 in sensitivity to methamphetamine and Zmynd11 in anxiety-like behavior. The combination of CFW mice, GBS and RNA-Sequencing constitutes a powerful approach to GWAS in mice.