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Diabetic Retinopathy Environment-Wide Association Study (EWAS) in NHANES 2005–2008

Blighe, K; Gurudas, S; Lee, Y; Sivaprasad, S; (2020) Diabetic Retinopathy Environment-Wide Association Study (EWAS) in NHANES 2005–2008. Journal of Clinical Medicine , 9 (11) , Article 3643. 10.3390/jcm9113643. Green open access

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Abstract

Several circulating biomarkers are reported to be associated with diabetic retinopathy (DR). However, their relative contributions to DR compared to known risk factors, such as hyperglycaemia, hypertension, and hyperlipidaemia, remain unclear. In this data driven study, we used novel models to evaluate the associations of over 400 laboratory parameters with DR compared to the established risk factors. Methods: we performed an environment-wide association study (EWAS) of laboratory parameters available in National Health and Nutrition Examination Survey (NHANES) 2007–2008 in individuals with diabetes with DR as the outcome (test set). We employed independent variable (feature) selection approaches, including parallelised univariate regression modelling, Principal Component Analysis (PCA), penalised regression, and RandomForest™. These models were replicated in NHANES 2005–2006 (replication set). Our test and replication sets consisted of 1025 and 637 individuals with available DR status and laboratory data respectively. Glycohemoglobin (HbA1c) was the strongest risk factor for DR. Our PCA-based approach produced a model that incorporated 18 principal components (PCs) that had an Area under the Curve (AUC) 0.796 (95% CI 0.761–0.832), while penalised regression identified a 9-feature model with 78.51% accuracy and AUC 0.74 (95% CI 0.72–0.77). RandomForest™ identified a 31-feature model with 78.4% accuracy and AUC 0.71 (95% CI 0.65–0.77). On grouping the selected variables in our RandomForest™, hyperglycaemia alone achieved AUC 0.72 (95% CI 0.68–0.76). The AUC increased to 0.84 (95% CI 0.78–0.9) when the model also included hypertension, hypercholesterolemia, haematocrit, renal, and liver function tests.

Type: Article
Title: Diabetic Retinopathy Environment-Wide Association Study (EWAS) in NHANES 2005–2008
Open access status: An open access version is available from UCL Discovery
DOI: 10.3390/jcm9113643
Publisher version: https://doi.org/10.3390/jcm9113643
Language: English
Additional information: This is an open access article distributed under the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: environment wide association study; diabetic retinopathy; hyperglycaemia; circulating biomarkers
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/10115184
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