title: Reporting phenotypes in mouse models when considering body size as a potential confounder.
abstract: Genotype-phenotype studies aim to identify causative relationships between genes and phenotypes. The International Mouse Phenotyping Consortium is a high throughput phenotyping program whose goal is to collect phenotype data for a knockout mouse strain of every protein coding gene. The scale of the project requires an automatic analysis pipeline to detect abnormal phenotypes, and disseminate the resulting gene-phenotype annotation data into public resources. A body weight phenotype is a common result of knockout studies. As body weight correlates with many other biological traits, this challenges the interpretation of related gene-phenotype associations. Co-correlation can lead to gene-phenotype associations that are potentially misleading. Here we use statistical modelling to account for body weight as a potential confounder to assess the impact. We find that there is a considerable impact on previously established gene-phenotype associations due to an increase in sensitivity as well as the confounding effect. We investigated the existing ontologies to represent this phenotypic information and we explored ways to ontologically represent the results of the influence of confounders on gene-phenotype associations. With the scale of data being disseminated within the high throughput programs and the range of downstream studies that utilise these data, it is critical to consider how we improve the quality of the disseminated data and provide a robust ontological representation.
authors: Mouse Informatics Group, Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire UK ; Social Genetic & Developmental Psychiatry, King's College London, London, UK.
authors: Anika
authors: A
authors: Oellrich
authors: Samples, Phenotypes and Ontologies, European Molecular Biology Laboratory-European Bioinformatics Institute, Hinxton, Cambridge UK.
authors: Terrence F
authors: TF
authors: Meehan
authors: Samples, Phenotypes and Ontologies, European Bioinformatics Institute (EMBL-EBI), European Molecular Biology Laboratory, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD UK.
authors: Helen
authors: H
authors: Parkinson
authors: Samples, Phenotypes and Ontologies, European Bioinformatics Institute (EMBL-EBI), European Molecular Biology Laboratory, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD UK ; The Centre for Therapeutic Target Validation, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD UK.
authors: Sirarat
authors: S
authors: Sarntivijai
authors: Mouse Genetics Project, Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire UK.
authors: Jacqueline K
authors: JK
authors: White
authors: Mouse Informatics Group, Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire UK.
authors: Natasha A
authors: 0000-0002-8404-2907
authors: NA
authors: Karp
mesh_terms: D000818:Animals; D049628:Body Size; D005260:Female; D063990:Gene Ontology; D005838:Genotype; D008297:Male; D051379:Mice; D023421:Models, Animal; D010641:Phenotype; D012015:Reference Standards