Phenotype risk scores identify patients with unrecognized Mendelian disease patterns

• DOI: 10.1126/science.aal4043
• Publication Date: 2018-03-15T19:50:46Z
• Authors: Lisa Bastarache; Jacob J. Hughey; Scott Hebbring; Joy Marlo; Wanke Zhao; Wanting T. Ho; Sara L. Van Driest; Tracy L. McGregor; Jonathan D. Mosley; Quinn S. Wells; Michael Temple; Andrea H. Ramirez; Robert Carroll; Travis Osterman; Todd Edwards; Douglas Ruderfer; Digna R. Velez Ed...; Rizwan Hamid; Joy Cogan; Andrew Glazer; Wei-Qi Wei; QiPing Feng; Murray Brilliant; Zhizhuang J. Zhao; Nancy J. Cox; Dan M. Roden; Joshua C. Denny
• Keywords: Phenotype; Risk Factors; DNA Mutational Analysis; Databases, Genetic; Genetic Diseases, Inborn; Electronic Health Records; Genetic Variation; Humans; Exome; Genetic Predisposition to Disease; Genetic Association Studies; 3. Good health

Hidden effects of Mendelian inheritance

Identifying the determinate factors of genetic disease has been quite successful for Mendelian inheritance of large-effect pathogenic variants. In these cases, two non- or low-functioning genes contribute to disease. However, Mendelian effects of lesser strength have generally been ignored when looking at genomic consequences in human health. Bastarache et al. used electronic records to identify the phenotypic effects of previously unidentified Mendelian variations. Their analysis suggests that individuals with undiagnosed Mendelian diseases may be more prevalent in the general population than assumed. Because of this, genetic analysis may be able to assist clinicians in arriving at a diagnosis.

Science , this issue p. 1233