ArticleGenome medicine2021
Clinical laboratory test-wide association scan of polygenic scores identifies biomarkers of complex disease.
Article in Genome medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers, 7 of them syntheses that pooled it.
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Who cites it
96 citing papers in PubMed, 7 syntheses or guidelines pooled it.
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- Sex hormones and reproductive factors with cardiac arrhythmia and ECG indices: a mendelian randomization study.BMC cardiovascular disorders · 2024Pooled it
- Leveraging pleiotropy identifies common-variant associations with selective IgA deficiency.Clinical immunology (Orlando, Fla.) · 2024Pooled it
- Multi-ancestry meta-analysis of tobacco use disorder identifies 461 potential risk genes and reveals associations with multiple health outcomes.Nature human behaviour · 2024Pooled it
- Cross-ancestry meta-analysis of opioid use disorder uncovers novel loci with predominant effects in brain regions associated with addiction.Nature neuroscience · 2022Pooled it
- Mendelian pathway analysis of laboratory traits reveals distinct roles for ciliary subcompartments in common disease pathogenesis.American journal of human genetics · 2021Pooled it
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- The MICOS Complex Regulates Mitochondrial Structure and Oxidative Stress During Age-Dependent Structural Deficits in the Kidney.bioRxiv : the preprint server for biology · 2026Article
36 more citing papers are in PubMed but not listed here.
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18 authors.
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Abstract
backgroundClinical 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.
methodsA 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.
resultsHeritability 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.
conclusionsPolygenic 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.
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