背景:深度学习有助于对身体成分进行大规模自动化成像评估。然而,身体成分生物标志物与医学表型的关联研究不足。全表型关联研究(PheWAS)技术搜索与生物标志物相关的医学表型。PheWAS整合成像生物标志物和电子健康记录(EHR)数据的大规模分析可以发现以前未报告的关联并验证预期的关联。在这里,我们使用PheWAS方法来确定基于腹部CT的骨骼肌指标与北美大型队列中医学表型的关联。
方法:使用自动深度学习管道从2012年至2018年的成人腹部CT扫描中测量骨骼肌指数(SMI;肌肉减少症的生物标志物)和骨骼肌密度(SMD;肌萎缩症的生物标志物)。使用患者性别和年龄作为协变量进行PheWAS的逻辑回归,以评估CT衍生的肌肉指标与611种常见EHR衍生的医学表型之间的关联。PheWASP值在Bonferroni校正阈值(α=0.05/1222)下被认为是显著的。
结果:17,646名成年人(平均年龄,包括56岁±19[SD];57.5%的女性)。CT来源的SMI与268种医学表型显著相关;SMD与340种医学表型显著相关。以前未报告的具有最高显著性的关联包括较高的SMI和降低的心律失常(OR[95%CI],0.59[0.55-0.64];P<0.0001),癫痫减少(或,0.59[0.50-0.70];P<0.0001),和升高的前列腺特异性抗原(OR,1.84[1.47-2.31];P<0.0001),和更高的SMD,褥疮溃疡减少(或,0.36[0.31-0.42];P<0.0001),睡眠障碍(或,0.39[0.32-0.47];P<0.0001),和骨髓炎(或,0.43[0.36-0.52];P<0.0001)。
结论:PheWAS方法揭示了以前未报道的CT衍生的肌肉减少症和肌肉骨化的生物标志物与EHR医学表型之间的关联。在人群规模上应用的高通量PheWAS技术可以产生与肌减少症和肌骨关节炎相关的研究假设,并且可以适应于研究其他成像生物标志物与数百种EHR医学表型的可能关联。
背景:美国国立卫生研究院,斯坦福AIMI-HAI试点拨款,StanfordPrecisionHealthandIntegratedDiagnostics,斯坦福心血管研究所,斯坦福数字健康中心,和斯坦福奈特-轩尼诗学者。
BACKGROUND: Deep learning facilitates large-scale automated imaging evaluation of body composition. However, associations of body composition biomarkers with medical phenotypes have been underexplored. Phenome-wide association
study (PheWAS) techniques search for medical phenotypes associated with biomarkers. A PheWAS integrating large-scale analysis of imaging biomarkers and electronic health record (EHR) data could discover previously unreported associations and validate expected associations. Here we use PheWAS methodology to determine the association of abdominal CT-based skeletal muscle metrics with medical phenotypes in a large North American cohort.
METHODS: An automated deep learning pipeline was used to measure skeletal muscle index (SMI; biomarker of myopenia) and skeletal muscle density (SMD; biomarker of
myosteatosis) from abdominal CT scans of adults between 2012 and 2018. A PheWAS was performed with logistic regression using patient sex and age as covariates to assess for associations between CT-derived muscle metrics and 611 common EHR-derived medical phenotypes. PheWAS P values were considered significant at a Bonferroni corrected threshold (α = 0.05/1222).
RESULTS: 17,646 adults (mean age, 56 years ± 19 [SD]; 57.5% women) were included. CT-derived SMI was significantly associated with 268 medical phenotypes; SMD with 340 medical phenotypes. Previously unreported associations with the highest magnitude of significance included higher SMI with decreased cardiac dysrhythmias (OR [95% CI], 0.59 [0.55-0.64]; P < 0.0001), decreased epilepsy (OR, 0.59 [0.50-0.70]; P < 0.0001), and increased elevated prostate-specific antigen (OR, 1.84 [1.47-2.31]; P < 0.0001), and higher SMD with decreased decubitus ulcers (OR, 0.36 [0.31-0.42]; P < 0.0001), sleep disorders (OR, 0.39 [0.32-0.47]; P < 0.0001), and osteomyelitis (OR, 0.43 [0.36-0.52]; P < 0.0001).
CONCLUSIONS: PheWAS methodology reveals previously unreported associations between CT-derived biomarkers of myopenia and
myosteatosis and EHR medical phenotypes. The high-throughput PheWAS technique applied on a population scale can generate research hypotheses related to myopenia and
myosteatosis and can be adapted to research possible associations of other imaging biomarkers with hundreds of EHR medical phenotypes.
BACKGROUND: National Institutes of Health, Stanford AIMI-HAI pilot grant, Stanford Precision Health and Integrated Diagnostics, Stanford Cardiovascular Institute, Stanford Center for Digital Health, and Stanford Knight-Hennessy Scholars.