Development and Evaluation of a Rules-based Algorithm for Primary Open-Angle Glaucoma in the VA Million Veteran Program

Nealon, Cari L.; Halladay, Christopher; Kinzy, Tyler G.; Simpson, Piana; Canania, Rachael L.; Anthony, Scott A.; Roncone, David P.; Rogers, Lea R Sawicki; Leber, Jenna N.; Dougherty, Jacquelyn M.; Sullivan, Jack; Wu, Wen‐Chih; Greenberg, Paul B.; Iyengar, Sudha K.; Crawford, Dana C.; Peachey, Neal S.; Bailey, Jessica N. Cooke

doi:10.1080/09286586.2021.1992784

Cited by 8 publications

(2 citation statements)

References 48 publications

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“…16 Rules-based algorithms have been successfully used within MVP to identify other ocular diseases including age-related macular degeneration 17 and primary open angle glaucoma. 18 To support our analysis, we developed a FECD phenotype algorithm based on International Classification of Diseases Clinical Modification (ICD-CM) codes and Current Procedural Terminology (CPT) codes to accurately identify FECD cases and controls within the VA Computerized Patient Record System (CPRS). 19 We used our FECD case-control algorithm to conduct a phenotype wide association study (PheWAS) for FECD.…”

mentioning

confidence: 99%

Association between Fuchs Endothelial Corneal Dystrophy, Diabetes Mellitus and Multimorbidity

Nealon

Halladay

Gorman

et al. 2022

Preprint

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Purpose: To assess risk for demographic variables and other health conditions that are associated with Fuchs endothelial corneal dystrophy (FECD). Methods: We developed a FECD case-control algorithm based on structured EHR data and accuracy confirmed by individual review of charts at three VA Medical Centers. This algorithm was applied to the Department of Veterans Affairs Million Veteran Program cohort from whom sex, genetic ancestry, comorbidities, diagnostic phecodes and laboratory values were extracted. Single and multiple variable logistic regression models were used to determine the association of these risk factors with FECD diagnosis. Results: Being a FECD case was associated with female sex, European genetic ancestry, and a greater number of comorbidities. Of 1417 diagnostic phecodes evaluated, 213 had a significant association with FECD, falling in both ocular and non-ocular conditions, including diabetes mellitus (DM). Five of 69 laboratory values were associated with FECD, with the direction of change for four being consistent with DM. Insulin dependency and type 1 DM raised risk to a greater degree than type 2 DM, like other microvascular diabetic complications. Conclusions: Female gender, European ancestry and multimorbidity increased FECD risk. Endocrine/metabolic clinic encounter codes as well as altered patterns of laboratory values support DM increasing FECD risk. Our results evoke a threshold model in which the FECD phenotype is intensified by DM and potentially other health conditions that alter corneal physiology. DM may modify FECD onset and encourage progression among susceptible individuals, suggesting that optimizing glucose control may be an effective preventative for FECD.

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confidence: 99%

Association between Fuchs Endothelial Corneal Dystrophy, Diabetes Mellitus and Multimorbidity

Nealon

Halladay

Gorman

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…16 Rule-based algorithms have been successfully used within MVP to identify other ocular diseases including age-related macular degeneration 17 and primary open-angle glaucoma. 18 To support our analysis, we developed a FECD phenotype algorithm based on International Classification of Diseases Clinical Modification codes and Current Procedural Terminology codes to accurately identify FECD cases and controls within the VA Computerized Patient Record System (CPRS). 19 We used our FECD case-control algorithm to conduct a phenotype-wide association study (PheWAS) for FECD.…”

mentioning

confidence: 99%

Association Between Fuchs Endothelial Corneal Dystrophy, Diabetes Mellitus, and Multimorbidity

Nealon

Halladay

Gorman

et al. 2023

Cornea

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Performance of Polygenic Risk Scores for Primary Open-Angle Glaucoma in Populations of African Descent

Chang-Wolf,

Kinzy,

Driessen

et al. 2024

JAMA Ophthalmol

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ImportancePrimary open-angle glaucoma (POAG) polygenic risk scores (PRSs) continue to be evaluated in primarily European-ancestry populations despite higher prevalence and worse outcomes in African-ancestry populations.ObjectiveTo evaluate how established POAG PRSs perform in African-ancestry samples from the Genetics in Glaucoma Patients of African Descent (GIGA), Genetics of Glaucoma in Individuals of African Descent (GGLAD), and Million Veteran Program (MVP) datasets and compare these with European-ancestry samples.Design, Setting, and ParticipantsThis was a multicenter, cross-sectional study of POAG cases and controls from Tanzania, South Africa, Nigeria, Ghana, and the US. Included were individuals of African descent from South Africa and Tanzania from the GIGA dataset; individuals of African descent from Ghana, Nigeria, and the US from the GGLAD dataset; and individuals of African or European descent from the US in the MVP dataset. Data were analyzed from January 2022 to July 2023.ExposuresThree PRSs derived from large meta-analyses of European and Asian populations, namely Gharahkhani et al (Gharahkhani PRS), Han et al (Han PRS), and Craig et al (Craig PRS).Main Outcomes and MeasuresOdds ratios (ORs) for POAG risk stratification comparing the highest and lowest quintiles; area under the receiver operating characteristic curve (AUROC), and liability coefficient of determination (R2) for the addition of PRS to a baseline of age, sex, and first 5 principal components.ResultsA total of 11 673 cases and 66 432 controls were included in this study across 7 ancestral groups. Mean (SD) age of the total participants was 76.9 (8.7) years, with 74 304 males (95.1%). The following were included in each dataset: GIGA (663 cases, 476 controls), GGLAD (1471 cases, 1482 controls), and MVP (9559 cases, 64 474 controls). Increases in ORs were found for the highest POAG risk quintile ranging from an OR of 1.68 (95% CI, 1.17-2.43) in Ghanaians to 7.05 (95% CI, 2.73-19.6) in the South African multiple ancestry group (which derives from at least 5 distinct ancestral groups: Khoisan, Bantus, Europeans, Indians, and Southeast Asians) with the Gharahkhani PRS. The Han PRS showed OR increases for the highest POAG risk quintile ranging from 2.27 (95% CI, 1.49-3.47) in African American individuals in the GGLAD dataset to 7.24 (95% CI, 6.47-8.12) in Europeans. The Craig PRS predicted OR increases in the highest quintile for all groups ranging from 1.51 (95% CI, 1.05-2.18) in Ghanaians to 6.31 (95% CI, 5.67-7.04) in Europeans. However, AUROC and R2 increases above baseline were lower for all African-ancestry compared with European-ancestry groups in the 3 tested PRSs.Conclusions and RelevanceIn this cross-sectional study, despite some improvements in OR-based risk stratification using the Gharahkhani PRSs, Han PRSs, and Craig PRSs, consistently lower improvements in AUROC and R2 for African-ancestry compared with European-ancestry groups highlight the need for risk prediction models tailored to diverse populations.

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Development and Evaluation of a Rules-based Algorithm for Primary Open-Angle Glaucoma in the VA Million Veteran Program

Cited by 8 publications

References 48 publications

Association between Fuchs Endothelial Corneal Dystrophy, Diabetes Mellitus and Multimorbidity

Association between Fuchs Endothelial Corneal Dystrophy, Diabetes Mellitus and Multimorbidity

Association Between Fuchs Endothelial Corneal Dystrophy, Diabetes Mellitus, and Multimorbidity

Performance of Polygenic Risk Scores for Primary Open-Angle Glaucoma in Populations of African Descent

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