title: Exploring causal networks underlying fat deposition and muscularity in pigs through the integration of phenotypic, genotypic and transcriptomic data.
abstract: BACKGROUND
  Joint modeling and analysis of phenotypic, genotypic and transcriptomic data have the potential to uncover the genetic control of gene activity and phenotypic variation, as well as shed light on the manner and extent of connectedness among these variables. Current studies mainly report associations, i.e. undirected connections among variables without causal interpretation. Knowledge regarding causal relationships among genes and phenotypes can be used to predict the behavior of complex systems, as well as to optimize management practices and selection strategies. Here, we performed a multistep procedure for inferring causal networks underlying carcass fat deposition and muscularity in pigs using multi-omics data obtained from an F2 Duroc x Pietrain resource pig population.
  
  
  RESULTS
  We initially explored marginal associations between genotypes and phenotypic and expression traits through whole-genome scans, and then, in genomic regions with multiple significant hits, we assessed gene-phenotype network reconstruction using causal structural learning algorithms. One genomic region on SSC6 showed significant associations with three relevant phenotypes, off-midline10th-rib backfat thickness, loin muscle weight, and average intramuscular fat percentage, and also with the expression of seven genes, including ZNF24, SSX2IP, and AKR7A2. The inferred network indicated that the genotype affects the three phenotypes mainly through the expression of several genes. Among the phenotypes, fat deposition traits negatively affected loin muscle weight.
  
  
  CONCLUSIONS
  Our findings shed light on the antagonist relationship between carcass fat deposition and lean meat content in pigs. In addition, the procedure described in this study has the potential to unravel gene-phenotype networks underlying complex phenotypes.
authors.affiliation: Department of Animal Sciences, University of Wisconsin-Madison, Madison, WI, 53706, USA. fpenagaricano@ufl.edu.|Present Address: Department of Animal Sciences, and University of Florida Genetics Institute, University of Florida, Gainesville, FL, 326111, USA. fpenagaricano@ufl.edu.
authors.forename: Francisco
authors.initials: F
authors.lastname: Peñagaricano
authors.affiliation: Department of Animal Sciences, University of Wisconsin-Madison, Madison, WI, 53706, USA. bvalente@wisc.edu.|Dairy Science, University of Wisconsin-Madison, Madison, WI, 53706, USA. bvalente@wisc.edu.
authors.forename: Bruno D
authors.initials: BD
authors.lastname: Valente
authors.affiliation: Department of Animal Science, Michigan State University, East Lansing, MI, 48824, USA. steibelj@msu.edu.
authors.forename: Juan P
authors.initials: JP
authors.lastname: Steibel
authors.affiliation: Department of Animal Science, Michigan State University, East Lansing, MI, 48824, USA. batesr@msu.edu.
authors.forename: Ronald O
authors.initials: RO
authors.lastname: Bates
authors.affiliation: Department of Animal Science, Michigan State University, East Lansing, MI, 48824, USA. ernstc@msu.edu.
authors.forename: Catherine W
authors.initials: CW
authors.lastname: Ernst
authors.affiliation: Department of Animal Sciences, University of Wisconsin-Madison, Madison, WI, 53706, USA. hkhatib@wisc.edu.
authors.forename: Hasan
authors.initials: H
authors.lastname: Khatib
authors.affiliation: Department of Animal Sciences, University of Wisconsin-Madison, Madison, WI, 53706, USA. grosa@wisc.edu.|Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI, 53706, USA. grosa@wisc.edu.
authors.forename: Guilherme J M
authors.initials: GJ
authors.lastname: Rosa
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000465:Algorithms; D000818:Animals; D005260:Female; D020869:Gene Expression Profiling; D005838:Genotype; D008297:Male; D008460:Meat; D009132:Muscles / Q000033:anatomy & histology / Q000378:metabolism*; D009929:Organ Size; D010641:Phenotype; D040641:Quantitative Trait Loci / Q000235:genetics; D013552:Swine / Q000033:anatomy & histology / Q000235:genetics*