Evaluation of primary open-angle glaucoma phenotype algorithm in African Americans from EAGLE BioVU.

<p>Definite cases were individuals whose POAG status could be determined with high likelihood. Potential cases were individuals whose medical records lacked sufficient information to make a definitive decision. Potential case results were calculated by including both potential and definite case numbers.</p><p>Evaluation of primary open-angle glaucoma phenotype algorithm in African Americans from EAGLE BioVU.</p

Extracting Primary Open-Angle Glaucoma from Electronic Medical Records for Genetic Association Studies

<div><p>Electronic medical records (EMRs) are being widely implemented for use in genetic and genomic studies. As a phenotypic rich resource, EMRs provide researchers with the opportunity to identify disease cohorts and perform genotype-phenotype association studies. The Epidemiologic Architecture for Genes Linked to Environment (EAGLE) study, as part of the Population Architecture using Genomics and Epidemiology (PAGE) I study, has genotyped more than 15,000 individuals of diverse genetic ancestry in BioVU, the Vanderbilt University Medical Center’s biorepository linked to a de-identified version of the EMR (EAGLE BioVU). Here we develop and deploy an algorithm utilizing data mining techniques to identify primary open-angle glaucoma (POAG) in African Americans from EAGLE BioVU for genetic association studies. The algorithm described here was designed using a combination of diagnostic codes, current procedural terminology billing codes, and free text searches to identify POAG status in situations where gold-standard digital photography cannot be accessed. The case algorithm identified 267 potential POAG subjects but underperformed after manual review with a positive predictive value of 51.6% and an accuracy of 76.3%. The control algorithm identified controls with a negative predictive value of 98.3%. Although the case algorithm requires more downstream manual review for use in large-scale studies, it provides a basis by which to extract a specific clinical subtype of glaucoma from EMRs in the absence of digital photographs.</p></div

Criteria and decision tree used to classify individuals in EAGLE BioVU as POAG cases or controls.

<p>(A) Flow diagram of phenotype algorithm for POAG cases and controls. (B) List of glaucoma ICD-9 codes (C) List of CPT codes for ophthalmology and general clinic procedures.</p

De-identified clinic notes extracted from the Synthetic Derivative.

<p>De-identified letters from the Vanderbilt Eye Institute’s ophthalmologists and optometrists extracted from the Synthetic Derivative. These letters represent the primary type of record used to verify POAG case status in EAGLE BioVU. It is an example of a definite case which has the specific clinical sub-type of glaucoma clearly stated and of a potential case which only includes a more general glaucoma diagnosis statement.</p

Published index variants for the <i>CDKN2B-AS1 region</i> associated with POAG or POAG associated trait and availability of these variants on the Metabochip.

<p>Shown are significant index variants which are listed on the NHGRI GWAS catalog and within PubMed. Included is the availability of the index variants on the Metabochip and summary results for the current studies association analysis of African Americans with POAG in the <i>CDKN2B-AS1</i> region.</p><p>Published index variants for the <i>CDKN2B-AS1 region</i> associated with POAG or POAG associated trait and availability of these variants on the Metabochip.</p

Distribution of -value changes for associations between clinical conditions and SNP rs1333049 for left) , middle) , and right) DEMOS.

<p>Distribution of -value changes for associations between clinical conditions and SNP rs1333049 for left) , middle) , and right) DEMOS.</p

Changes in p-values for associations between clinical conditions and SNP rs1333049 presented as a QQ-plot for left) , middle) , and right) DEMOS.

<p>Descriptions of the annotated conditions in the plots are provided in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0053875#pone-0053875-t005" target="_blank">Table 5</a>.</p

Full Diagnosis Count information retained.

<p>Full Diagnosis Count information retained.</p

Fucus sp.

<p>Descriptions of the annotated conditions in the plots are provided in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0053875#pone-0053875-t005" target="_blank">Table 5</a>.</p

Results of anonymization on PheWAS Analysis for six SNPs.

<p>, , and are the Demonstration group when anonymized, extracted from the BioVU anonymization, and extracted from the SD anonymization, respectively. Original is the number of significant associations (p 0.05) found in the PheWAS when conducted on pre-anonymized data. Identical is the number of associations which were the same between studies. Lost is the number of associations that were lost in the anonymized study. False is the number of associations that were determined as significant in the new study but were not in the original.</p