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Clinical laboratory test-wide association scan of polygenic scores identifies biomarkers of complex disease

التفاصيل البيبلوغرافية
العنوان: Clinical laboratory test-wide association scan of polygenic scores identifies biomarkers of complex disease
المؤلفون: Jessica K. Dennis, Julia M. Sealock, Peter Straub, Younga H. Lee, Donald Hucks, Ky’Era Actkins, Annika Faucon, Yen-Chen Anne Feng, Tian Ge, Slavina B. Goleva, Maria Niarchou, Kritika Singh, Theodore Morley, Jordan W. Smoller, Douglas M. Ruderfer, Jonathan D. Mosley, Guanhua Chen, Lea K. Davis
المصدر: Genome Medicine, Vol 13, Iss 1, Pp 1-16 (2021)
بيانات النشر: BMC, 2021.
سنة النشر: 2021
المجموعة: LCC:Medicine
LCC:Genetics
مصطلحات موضوعية: Electronic health records, Population genetics, Genetic epidemiology, Biomarkers, Medicine, Genetics, QH426-470
الوصف: Abstract Background Clinical laboratory (lab) tests are used in clinical practice to diagnose, treat, and monitor disease conditions. Test results are stored in electronic health records (EHRs), and a growing number of EHRs are linked to patient DNA, offering unprecedented opportunities to query relationships between genetic risk for complex disease and quantitative physiological measurements collected on large populations. Methods A total of 3075 quantitative lab tests were extracted from Vanderbilt University Medical Center’s (VUMC) EHR system and cleaned for population-level analysis according to our QualityLab protocol. Lab values extracted from BioVU were compared with previous population studies using heritability and genetic correlation analyses. We then tested the hypothesis that polygenic risk scores for biomarkers and complex disease are associated with biomarkers of disease extracted from the EHR. In a proof of concept analyses, we focused on lipids and coronary artery disease (CAD). We cleaned lab traits extracted from the EHR performed lab-wide association scans (LabWAS) of the lipids and CAD polygenic risk scores across 315 heritable lab tests then replicated the pipeline and analyses in the Massachusetts General Brigham Biobank. Results Heritability estimates of lipid values (after cleaning with QualityLab) were comparable to previous reports and polygenic scores for lipids were strongly associated with their referent lipid in a LabWAS. LabWAS of the polygenic score for CAD recapitulated canonical heart disease biomarker profiles including decreased HDL, increased pre-medication LDL, triglycerides, blood glucose, and glycated hemoglobin (HgbA1C) in European and African descent populations. Notably, many of these associations remained even after adjusting for the presence of cardiovascular disease and were replicated in the MGBB. Conclusions Polygenic risk scores can be used to identify biomarkers of complex disease in large-scale EHR-based genomic analyses, providing new avenues for discovery of novel biomarkers and deeper understanding of disease trajectories in pre-symptomatic individuals. We present two methods and associated software, QualityLab and LabWAS, to clean and analyze EHR labs at scale and perform a Lab-Wide Association Scan.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1756-994X
Relation: https://doaj.org/toc/1756-994X
DOI: 10.1186/s13073-020-00820-8
URL الوصول: https://doaj.org/article/6757a64b9b8c477ebf816cd361461549
رقم الأكسشن: edsdoj.6757a64b9b8c477ebf816cd361461549
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:1756994X
DOI:10.1186/s13073-020-00820-8