@article {29,
	title = {Phenotype risk scores identify patients with unrecognized Mendelian disease patterns.},
	journal = {Science},
	volume = {359},
	year = {2018},
	month = {2018 Mar 16},
	pages = {1233-1239},
	abstract = {<p>Genetic association studies often examine features independently, potentially missing subpopulations with multiple phenotypes that share a single cause. 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.</p>},
	keywords = {Databases, Genetic, DNA Mutational Analysis, Electronic Health Records, Exome, Genetic Association Studies, Genetic Diseases, Inborn, Genetic Predisposition to Disease, Genetic Variation, Humans, Phenotype, Risk Factors},
	issn = {1095-9203},
	doi = {10.1126/science.aal4043},
	author = {Bastarache, Lisa and Hughey, Jacob J and Hebbring, Scott and Marlo, Joy and Zhao, Wanke and Ho, Wanting T and Van Driest, Sara L and McGregor, Tracy L and Mosley, Jonathan D and Wells, Quinn S and Temple, Michael and Ramirez, Andrea H and Carroll, Robert and Osterman, Travis and Edwards, Todd and Ruderfer, Douglas and Velez Edwards, Digna R and Hamid, Rizwan and Cogan, Joy and Glazer, Andrew and Wei, Wei-Qi and Feng, QiPing and Brilliant, Murray and Zhao, Zhizhuang J and Cox, Nancy J and Roden, Dan M and Denny, Joshua C}
}
