Common genetic variation associated with Mendelian disease severity revealed through cryptic phenotype analysis.

ABSTRACT: Clinical heterogeneity is common in Mendelian disease, but small sample sizes make it difficult to identify specific contributing factors. However, if a disease represents the severely affected extreme of a spectrum of phenotypic variation, then modifier effects may be apparent within a larger subset of the population. Analyses that take advantage of this full spectrum could have substantially increased power. To test this, we developed cryptic phenotype analysis, a model-based approach that infers quantitative traits that capture disease-related phenotypic variability using qualitative symptom data. By applying this approach to 50 Mendelian diseases in two cohorts, we identify traits that reliably quantify disease severity. We then conduct genome-wide association analyses for five of the

SUBMITTER: Blair DR 

PROVIDER: S-EPMC9237040 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature