A longitudinal footprint of genetic epilepsies using automated electronic medical record interpretation.
A longitudinal footprint of genetic epilepsies using automated electronic medical record interpretation.
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DOI：
10.1038/s41436-020-0923-1
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发表时间：
2020-12
期刊：
影响因子：
--
通讯作者：
Helbig I
中科院分区：
文献类型：
--
作者：
Ganesan S;Galer PD;Helbig KL;McKeown SE;O'Brien M;Gonzalez AK;Felmeister AS;Khankhanian P;Ellis CA;Helbig I
儿童癫痫有很强的遗传因素，但许多遗传病因的疾病轨迹仍然未知。电子病历 (EMR) 数据有可能允许分析纵向临床信息，但这尚未得到探索。我们分析了 658 名已知或推测患有遗传性癫痫患者的 62,104 名患者的医疗服务提供者输入的神经学诊断。为了统一临床术语，我们将临床描述符映射到人类表型本体 (HPO) 术语，并推断出更高级别的表型概念。然后，我们将所得的 286,085 个 HPO 项分入 100 个 3 个月的时间间隔，并评估每个间隔的基因-表型关联。我们分析了每位患者 6.9 年的中位随访时间和累计 3251 个患者年。校正多项测试后，我们发现“癫痫持续状态”与 SCN1A 在 1.0 年时显着相关，“严重智力障碍”与 PURA 在 9.75 年时显着相关，“婴儿痉挛症”和“癫痫痉挛”与 STXBP1 在 0.5 年时显着相关。确定的关联反映了这些病症的已知临床特征，并且手动图表审查排除了提供者偏差。纵向疾病史的某些方面可以通过 EMR 数据重建，并揭示显着的基因-表型关联，即使在密切相关的条件下也是如此。基因特异性 EMR 足迹可以实现结果研究和临床决策支持。
Childhood epilepsies have a strong genetic contribution, but the disease trajectory for many genetic etiologies remains unknown. Electronic medical record (EMR) data potentially allow for the analysis of longitudinal clinical information but this has not yet been explored. We analyzed provider-entered neurological diagnoses made at 62,104 patient encounters from 658 individuals with known or presumed genetic epilepsies. To harmonize clinical terminology, we mapped clinical descriptors to Human Phenotype Ontology (HPO) terms and inferred higher-level phenotypic concepts. We then binned the resulting 286,085 HPO terms to 100 3-month time intervals and assessed gene–phenotype associations at each interval. We analyzed a median follow-up of 6.9 years per patient and a cumulative 3251 patient years. Correcting for multiple testing, we identified significant associations between “Status epilepticus” with SCN1A at 1.0 years, “Severe intellectual disability” with PURA at 9.75 years, and “Infantile spasms” and “Epileptic spasms” with STXBP1 at 0.5 years. The identified associations reflect known clinical features of these conditions, and manual chart review excluded provider bias. Some aspects of the longitudinal disease histories can be reconstructed through EMR data and reveal significant gene–phenotype associations, even within closely related conditions. Gene-specific EMR footprints may enable outcome studies and clinical decision support.
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影响因子：
3.2
作者：
Hardjojo A;Gunachandran A;Pang L;Abdullah MRB;Wah W;Chong JWC;Goh EH;Teo SH;Lim G;Lee ML;Hsu W;Lee V;Chen MI;Wong F;Phang JSK
通讯作者：
Phang JSK
影响因子：
64.8
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Iossifov, Ivan;O'Roak, Brian J.;Sanders, Stephan J.;Ronemus, Michael;Krumm, Niklas;Levy, Dan;Stessman, Holly A.;Witherspoon, Kali T.;Vives, Laura;Patterson, Karynne E.;Smith, Joshua D.;Paeper, Bryan;Nickerson, Deborah A.;Dea, Jeanselle;Dong, Shan;Gonzalez, Luis E.;Mandell, Jeffrey D.;Mane, Shrikant M.;Murtha, Michael T.;Sullivan, Catherine A.;Walker, Michael F.;Waqar, Zainulabedin;Wei, Liping;Willsey, A. Jeremy;Yamrom, Boris;Lee, Yoon-ha;Grabowska, Ewa;Dalkic, Ertugrul;Wang, Zihua;Marks, Steven;Andrews, Peter;Leotta, Anthony;Kendall, Jude;Hakker, Inessa;Rosenbaum, Julie;Ma, Beicong;Rodgers, Linda;Troge, Jennifer;Narzisi, Giuseppe;Yoon, Seungtai;Schatz, Michael C.;Ye, Kenny;McCombie, W. Richard;Shendure, Jay;Eichler, Evan E.;State, Matthew W.;Wigler, Michael
通讯作者：
Wigler, Michael
影响因子：
8
作者：
Barbaresi, William J.;Colligan, Robert C.;Katusic, Slavica K.
通讯作者：
Katusic, Slavica K.
影响因子：
64.8
作者：
通讯作者：
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影响因子：
14.5
作者：
Harkin, Louise A.;McMahon, Jacinta M.;Scheffer, Ingrid E.
通讯作者：
Scheffer, Ingrid E.