Phenotype risk scores identify patients with unrecognized Mendelian disease patterns.
Phenotype risk scores identify patients with unrecognized Mendelian disease patterns.
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DOI：
10.1126/science.aal4043
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发表时间：
2018-03-16
期刊：
影响因子：
--
通讯作者：
Denny JC
中科院分区：
文献类型：
--
作者：
Bastarache L;Hughey JJ;Hebbring S;Marlo J;Zhao W;Ho WT;Van Driest SL;McGregor TL;Mosley JD;Wells QS;Temple M;Ramirez AH;Carroll R;Osterman T;Edwards T;Ruderfer D;Velez Edwards DR;Hamid R;Cogan J;Glazer A;Wei WQ;Feng Q;Brilliant M;Zhao ZJ;Cox NJ;Roden DM;Denny JC
遗传关联研究经常独立地检查特征，可能会遗漏具有共享单一原因的多种表型的亚群。我们描述了一种基于孟德尔疾病描述的模式聚集表型的方法。我们将1204种孟德尔疾病的临床特征映射为从电子健康记录（EHR）中捕获的表型，并将这些证据总结为表型风险评分（PheRS）。在最初的验证中，PheRS区分了五种孟德尔疾病的病例和对照。将PheRS应用于21,701个基因分型个体，发现了18种与孟德尔疾病一致的罕见变异和表型的关联。在16名患者中，罕见的基因变异与器官移植等严重后果有关。PheRS可以增加罕见变异的解释，并可能确定具有不同遗传原因的常见疾病患者亚群。
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 based on patterns described by Mendelian diseases. We mapped the clinical features of 1,204 Mendelian diseases into phenotypes captured from the electronic health record (EHR) and summarized this evidence as phenotype risk scores (PheRS). In an initial validation, PheRS distinguished cases and controls of five Mendelian diseases. Applying PheRS to 21,701 genotyped individuals uncovered 18 associations with 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.
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影响因子：
46.9
作者：
通讯作者：
--
DOI：
10.1146/annurev-genom-090314-024956
发表时间：
2016-08-31
影响因子：
8.7
作者：
Denny JC;Bastarache L;Roden DM
通讯作者：
Roden DM
影响因子：
14.9
作者：
Köhler S;Doelken SC;Mungall CJ;Bauer S;Firth HV;Bailleul-Forestier I;Black GC;Brown DL;Brudno M;Campbell J;FitzPatrick DR;Eppig JT;Jackson AP;Freson K;Girdea M;Helbig I;Hurst JA;Jähn J;Jackson LG;Kelly AM;Ledbetter DH;Mansour S;Martin CL;Moss C;Mumford A;Ouwehand WH;Park SM;Riggs ER;Scott RH;Sisodiya S;Van Vooren S;Wapner RJ;Wilkie AO;Wright CF;Vulto-van Silfhout AT;de Leeuw N;de Vries BB;Washingthon NL;Smith CL;Westerfield M;Schofield P;Ruef BJ;Gkoutos GV;Haendel M;Smedley D;Lewis SE;Robinson PN
通讯作者：
Robinson PN
影响因子：
30.8
作者：
Kircher, Martin;Witten, Daniela M.;Jain, Preti;O'Roak, Brian J.;Cooper, Gregory M.;Shendure, Jay
通讯作者：
Shendure, Jay
影响因子：
3.7
作者：
Crawford DC;Crosslin DR;Tromp G;Kullo IJ;Kuivaniemi H;Hayes MG;Denny JC;Bush WS;Haines JL;Roden DM;McCarty CA;Jarvik GP;Ritchie MD
通讯作者：
Ritchie MD