title: Genome-wide association study of behavioral, physiological and gene expression traits in outbred CFW mice.
abstract: Although mice are the most widely used mammalian 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 in comparison 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 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.
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, Illinois, USA.|Department of Psychology, Middlebury College, Middlebury, Vermont, USA.|Program in Neuroscience, Middlebury College, Middlebury, Vermont, USA.
authors.forename: Clarissa C
authors.initials: CC
authors.lastname: Parker
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, Illinois, USA.|Natural History Museum of Denmark, Copenhagen University, Copenhagen, Denmark.
authors.forename: Shyam
authors.identifier: 0000-0002-2004-6810
authors.initials: S
authors.lastname: Gopalakrishnan
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, Illinois, USA.|AncestryDNA, San Francisco, California, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Carbonetto
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, Illinois, USA.
authors.forename: Natalia M
authors.initials: NM
authors.lastname: Gonzales
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, Illinois, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Leung
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, Illinois, USA.
authors.forename: Yeonhee J
authors.initials: YJ
authors.lastname: Park
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, Illinois, USA.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Aryee
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, Illinois, USA.
authors.forename: Joe
authors.initials: J
authors.lastname: Davis
authors.affiliation: Department of Biobehavioral Health, Pennsylvania State University, University Park, Pennsylvania, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Blizard
authors.affiliation: Center for Musculoskeletal Research, University of Rochester, Rochester, New York, USA.|Department of Orthopedics and Rehabilitation, University of Rochester, Rochester, New York, USA.
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Ackert-Bicknell
authors.affiliation: School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK.
authors.forename: Arimantas
authors.initials: A
authors.lastname: Lionikas
authors.affiliation: Department of Genetics, Stanford University, Palo Alto, California, USA.|Department of Biology, Stanford University, Palo Alto, California, USA.|Howard Hughes Medical Institute, Stanford University, Palo Alto, California, USA.
authors.forename: Jonathan K
authors.initials: JK
authors.lastname: Pritchard
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, Illinois, USA.|Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, Illinois, USA.|Department of Psychiatry, University of California, San Diego, La Jolla, California, USA.|Institute for Genomic Medicine, University of California, San Diego, La Jolla, California, USA.
authors.forename: Abraham A
authors.identifier: 0000-0003-3634-0747
authors.initials: AA
authors.lastname: Palmer
mesh_terms: D000818:Animals; D021461:Animals, Outbred Strains / Q000235:genetics*; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000378:metabolism; D005786:Gene Expression Regulation; D005819:Genetic Markers / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D051379:Mice; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics*
chemical_list: D005819:Genetic Markers