title: A GWAS assessment of the contribution of genomic imprinting to the variation of body mass index in mice.
abstract: BACKGROUND
  Genomic imprinting is an epigenetic mechanism that can lead to differential gene expression depending on the parent-of-origin of a received allele. While most studies on imprinting address its underlying molecular mechanisms or attempt at discovering genomic regions that might be subject to imprinting, few have focused on the amount of phenotypic variation contributed by such epigenetic process. In this report, we give a brief review of a one-locus imprinting model in a quantitative genetics framework, and provide a decomposition of the genetic variance according to this model. Analytical deductions from the proposed imprinting model indicated a non-negligible contribution of imprinting to genetic variation of complex traits. Also, we performed a whole-genome scan analysis on mouse body mass index (BMI) aiming at revealing potential consequences when existing imprinting effects are ignored in genetic analysis.
  
  
  RESULTS
  10,021 SNP markers were used to perform a whole-genome single marker regression on mouse BMI using an additive and an imprinting model. Markers significant for imprinting indicated that BMI is subject to imprinting. Marked variance changed from 1.218 ×10(-4) to 1.842 ×10(-4) when imprinting was considered in the analysis, implying that one third of marked variance would be lost if existing imprinting effects were not accounted for. When both marker and pedigree information were used, estimated heritability increased from 0.176 to 0.195 when imprinting was considered.
  
  
  CONCLUSIONS
  When a complex trait is subject to imprinting, using an additive model that ignores this phenomenon may result in an underestimate of additive variability, potentially leading to wrong inferences about the underlying genetic architecture of that trait. This could be a possible factor explaining part of the missing heritability commonly observed in genome-wide association studies (GWAS).
authors.affiliation: Department of Animal Sciences, University of Wisconsin - Madison, 1675 Observatory Dr., Madison, 53706, WI, USA. yhu32@wisc.edu.
authors.forename: Yaodong
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Animal Sciences, University of Wisconsin - Madison, 1675 Observatory Dr., Madison, 53706, WI, USA. grosa@wisc.edu.|Department of Biostatistics and Medical Informatics, University of Wisconsin - Madison, 600 Highland Avenue, Madison, 53792, WI, USA. grosa@wisc.edu.
authors.forename: Guilherme Jm
authors.initials: GJ
authors.lastname: Rosa
authors.affiliation: Department of Animal Sciences, University of Wisconsin - Madison, 1675 Observatory Dr., Madison, 53706, WI, USA. gianola@ansci.wisc.edu.|Department of Biostatistics and Medical Informatics, University of Wisconsin - Madison, 600 Highland Avenue, Madison, 53792, WI, USA. gianola@ansci.wisc.edu.|Department of Dairy Science, University of Wisconsin - Madison, 1675 Observatory Dr., Madison, 53706, WI, USA. gianola@ansci.wisc.edu.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gianola
mesh_terms: D000465:Algorithms; D000483:Alleles; D000818:Animals; D015992:Body Mass Index; D001835:Body Weight / Q000235:genetics*; D005819:Genetic Markers; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D018392:Genomic Imprinting; D051379:Mice; D008957:Models, Genetic; D010641:Phenotype; D040641:Quantitative Trait Loci; D019655:Quantitative Trait, Heritable; D015203:Reproducibility of Results
chemical_list: D005819:Genetic Markers