title: Genetic Variation in the Social Environment Contributes to Health and Disease.
abstract: Assessing the impact of the social environment on health and disease is challenging. As social effects are in part determined by the genetic makeup of social partners, they can be studied from associations between genotypes of one individual and phenotype of another (social genetic effects, SGE, also called indirect genetic effects). For the first time we quantified the contribution of SGE to more than 100 organismal phenotypes and genome-wide gene expression measured in laboratory mice. We find that genetic variation in cage mates (i.e. SGE) contributes to variation in organismal and molecular measures related to anxiety, wound healing, immune function, and body weight. Social genetic effects explained up to 29% of phenotypic variance, and for several traits their contribution exceeded that of direct genetic effects (effects of an individual's genotypes on its own phenotype). Importantly, we show that ignoring SGE can severely bias estimates of direct genetic effects (heritability). Thus SGE may be an important source of "missing heritability" in studies of complex traits in human populations. In summary, our study uncovers an important contribution of the social environment to phenotypic variation, sets the basis for using SGE to dissect social effects, and identifies an opportunity to improve studies of direct genetic effects.
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, United Kingdom.
authors.forename: Amelie
authors.identifier: 0000-0003-2448-0283
authors.initials: A
authors.lastname: Baud
authors.affiliation: Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
authors.forename: Megan K
authors.initials: MK
authors.lastname: Mulligan
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, United Kingdom.
authors.forename: Francesco Paolo
authors.initials: FP
authors.lastname: Casale
authors.affiliation: Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
authors.forename: Jesse F
authors.initials: JF
authors.lastname: Ingels
authors.affiliation: Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
authors.forename: Casey J
authors.initials: CJ
authors.lastname: Bohl
authors.affiliation: AP-HP, Hôpital Lariboisière, Department of Biochemistry, INSERM U942, Paris, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Callebert
authors.affiliation: AP-HP, Hôpital Lariboisière, Department of Biochemistry, INSERM U942, Paris, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Launay
authors.affiliation: Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom.
authors.forename: Jon
authors.initials: J
authors.lastname: Krohn
authors.affiliation: INRA, UMR 1388 GenPhySE, Castanet Tolosan, France.
authors.forename: Andres
authors.initials: A
authors.lastname: Legarra
authors.affiliation: Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Williams
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, United Kingdom.
authors.forename: Oliver
authors.initials: O
authors.lastname: Stegle
mesh_terms: D000818:Animals; D001835:Body Weight / Q000235:genetics; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D007109:Immunity / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D019655:Quantitative Trait, Heritable; D012931:Social Environment; D014945:Wound Healing / Q000235:genetics