Phenotype Similarity Regression for Identifying the Genetic Determinants of Rare Diseases.

ABSTRACT: Rare genetic disorders, which can now be studied systematically with affordable genome sequencing, are often caused by high-penetrance rare variants. Such disorders are often heterogeneous and characterized by abnormalities spanning multiple organ systems ascertained with variable clinical precision. Existing methods for identifying genes with variants responsible for rare diseases summarize phenotypes with unstructured binary or quantitative variables. The Human Phenotype Ontology (HPO) allows composite phenotypes to be represented systematically but association methods accounting for the ontological relationship between HPO terms do not exist. We present a Bayesian method to model the association between an HPO-coded patient phenotype and genotype. Our method estimates the probability of

SUBMITTER: Greene D 

PROVIDER: S-EPMC4827100 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature