Phenotype risk scores identify patients with unrecognized Mendelian disease patterns

We describe an approach that aggregates phenotypes on the basis of patterns described by Mendelian diseases. We mapped the clinical features of 1204 Mendelian diseases into phenotypes captured from the electronic health record (EHR) and summarized this evidence as phenotype risk scores (PheRSs). In an initial validation, PheRS distinguished cases and controls of five Mendelian diseases. Applying PheRS to 21,701 genotyped individuals uncovered 18 associations between rare variants and phenotypes consistent with Mendelian diseases. In 16 patients, the rare genetic variants were associated with severe outcomes such as organ transplants. PheRS can augment rare-variant interpretation and may identify subsets of patients with distinct genetic causes for common diseases.

Source: ScienceNOW - March 15, 2018 Category: Science Authors: Bastarache, L., Hughey, J. J., Hebbring, S., Marlo, J., Zhao, W., Ho, W. T., Van Driest, S. L., McGregor, T. L., Mosley, J. D., Wells, Q. S., Temple, M., Ramirez, A. H., Carroll, R., Osterman, T., Edwards, T., Ruderfer, D., Velez Edwards, D. R., Hamid, R. Tags: Genetics r-articles Source Type: news