Genetic mutations associated with susceptibility to perioperative complications in a longitudinal biorepository with integrated genomic and electronic health records
Genetic mutations associated with susceptibility to perioperative complications in a longitudinal biorepository with integrated genomic and electronic health records
复制标题
DOI：
10.1016/j.bja.2020.08.009
复制
发表时间：
2020-12-01
影响因子：
9.8
通讯作者：
Douville, Christopher B.
中科院分区：
文献类型：
--
作者：
Douville, Nicholas J.;Kheterpal, Sachin;Douville, Christopher B.
背景资料：可以利用现有的遗传信息来识别可能影响其围手术期护理的疾病的易感性患者，但临床医生通常接触有限，并且没有接受过将这些信息置于背景中的培训。我们确定了患者的遗传易感性麻醉并发症使用围手术期biorepository和特点的一致性与现有diagnosis.Methods：成人患者接受手术，从2012年到2017年密歇根州医学同意基因分型。基因型与电子健康记录（EHR）相结合。我们回顾性地描述了与丁酰胆碱酯酶缺乏、因子V莱顿和恶性高热相关的变异频率，这三个药物遗传学因素具有围手术期影响。我们计算的百分比纯合子和杂合子的每一个已被诊断为以前和EHR的调查结果相一致的predisposition.Results：遗传数据分析显示，25的40 769（0.1%）患者是纯合子和1918（4.7%）是杂合子与丁酰胆碱酯酶缺乏症相关的突变。在纯合子个体中，14例（56%）携带预先存在的诊断。对于因子V Leiden，29例（0.1%）为纯合型，2153例（5.3%）为杂合型。在纯合子个体中，3例（10%）通过EHR衍生表型诊断，6例（21%）通过临床医生审查诊断。在一部分患者中评估恶性高热。我们检测到两名患者的相关突变。结论：我们使用为临床医生使用而设计的开源脚本确定了围手术期并发症的遗传易感性患者。我们验证了这一应用程序在回顾性分析的三个条件下具有良好的特征遗传，并表明，并不是所有的遗传易感性记录在EHR。
Background: Existing genetic information can be leveraged to identify patients with susceptibilities to conditions that might impact their perioperative care, but clinicians generally have limited exposure and are not trained to contextualise this information. We identified patients with genetic susceptibilities to anaesthetic complications using a perioperative biorepository and characterised the concordance with existing diagnoses.Methods: Adult patients undergoing surgery within Michigan Medicine from 2012 to 2017 were consented for genotyping. Genotypes were integrated with the electronic health record (EHR). We retrospectively characterised frequencies of variants associated with butyrylcholinesterase deficiency, factor V Leiden, and malignant hyperthermia, three pharmacogenetic factors with perioperative implications. We calculated the percentage homozygous and heterozygous for each that had been diagnosed previously and searched for EHR findings consistent with a predisposition.Results: Analysis of genetic data revealed that 25 out of 40 769 (0.1%) patients were homozygous and 1918 (4.7%) were heterozygous for mutations associated with butyrylcholinesterase deficiency. Of the homozygous individuals, 14 (56%) carried a pre-existing diagnosis. For factor V Leiden, 29 (0.1%) were homozygous and 2153 (5.3%) heterozygous. Of the homozygous individuals, three (10%) were diagnosed by EHR-derived phenotype and six (21%) by clinician review. Malignant hyperthermia was assessed in a subset of patients. We detected two patients with associated mutations. Neither carried clinical diagnoses.Conclusions: We identified patients with genetic susceptibility to perioperative complications using an open source script designed for clinician use. We validated this application in a retrospective analysis for three conditions with well-characterised inheritance, and showed that not all genetic susceptibilities were documented in the EHR.