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

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.

SUBMITTER: Blighe K

PROVIDER: S-EPMC7696981 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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

Blighe Kevin K Gurudas Sarega S Lee Ying Y Sivaprasad Sobha S

Journal of clinical medicine 20201112 11

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 ava ...[more]

PMID: 33198349

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Project description:BackgroundType 2 Diabetes (T2D) and other chronic diseases are caused by a complex combination of many genetic and environmental factors. Few methods are available to comprehensively associate specific physical environmental factors with disease. We conducted a pilot Environmental-Wide Association Study (EWAS), in which epidemiological data are comprehensively and systematically interpreted in a manner analogous to a Genome Wide Association Study (GWAS).Methods and findingsWe performed multiple cross-sectional analyses associating 266 unique environmental factors with clinical status for T2D defined by fasting blood sugar (FBG) concentration > or =126 mg/dL. We utilized available Centers for Disease Control (CDC) National Health and Nutrition Examination Survey (NHANES) cohorts from years 1999 to 2006. Within cohort sample numbers ranged from 503 to 3,318. Logistic regression models were adjusted for age, sex, body mass index (BMI), ethnicity, and an estimate of socioeconomic status (SES). As in GWAS, multiple comparisons were controlled and significant findings were validated with other cohorts. We discovered significant associations for the pesticide-derivative heptachlor epoxide (adjusted OR in three combined cohorts of 1.7 for a 1 SD change in exposure amount; p<0.001), and the vitamin gamma-tocopherol (adjusted OR 1.5; p<0.001). Higher concentrations of polychlorinated biphenyls (PCBs) such as PCB170 (adjusted OR 2.2; p<0.001) were also found. Protective factors associated with T2D included beta-carotenes (adjusted OR 0.6; p<0.001).Conclusions and significanceDespite difficulty in ascertaining causality, the potential for novel factors of large effect associated with T2D justify the use of EWAS to create hypotheses regarding the broad contribution of the environment to disease. Even in this study based on prior collected epidemiological measures, environmental factors can be found with effect sizes comparable to the best loci yet found by GWAS.

Project description:BackgroundArterial stiffness has been shown to be an independent risk factor for adverse events and all-cause mortality in patients. Although PWV is the gold standard for pulse wave velocity, its application in clinical practice is limited by the high cost and complexity. ePwv is a new, simple, non-invasive indicator of arterial stiffness. The aim of this study was to assess the relationship between ePwv and all-cause mortality in patients with coronary artery disease.MethodsThis is a cohort study, selected from NHANES 2005 to 2008, 402 patients with coronary artery disease were included. The ePWV was divided into two groups and KM survival curves were used to calculate cumulative mortality in patients with coronary artery disease. Restricted cubic spline were used to represent the relationship between ePWV and all-cause mortality in patients with coronary artery disease. Cox regression was used to diagnose the relationship between ePwv and all-cause mortality.ResultsThe mean age of the study subjects was 68.5 ± 11.8 years, of which 282 (70.1%) were men and 120 (29.9%) were women. During 180 months of follow-up, 160 all-cause mortality occurred. KM survival curves indicated that all-cause mortality increased with increasing ePWV. The relationship between ePWV and all-cause mortality in patients with coronary artery disease was verified by cox models. Patients in higher ePWV tertile tended to have higher all-cause mortality. After complete multivariate adjustment, an increase in ePWV was positively associated with all-cause mortality (HR = 1.180, 95% confidence interval (CI): 1.056-1.320). The multivariate-adjusted HR and 95% CI for the highest ePWV tertile was 1.582 (95% CI: 0.968-2.587) compared to the lowest tertile. In addition, the association between ePWV and mortality was visualized employing restricted spline curves, in which we found curves indicating a possible threshold for the effect of ePWV on all-cause mortality, with HR less than 1 when ePWV was less than 11.15 m/s; thereafter, there was a tendency for HR to increase with enhanced ePWV. Subgroup analysis showed that the correlation between ePWV and mortality persisted in population subgroups.ConclusionOur findings suggest that higher ePWV is associated with increased all-cause mortality in patients with coronary artery disease, particularly when ePWV exceeds 11.15 m/s.

Dataset Information

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

Publications

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

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