BackgroundGlaucoma is a leading cause of blindness in developed countries. Primary open-angle glaucoma (POAG), the most prevalent clinical subtype of glaucoma in the United States, affects African Americans at a higher rate compared with European Americans. Risk factors identified for POAG include increased age and family history, which coupled with heritability estimates, suggest this complex condition is associated with genetic and environmental factors. To date, several genome-wide studies have identified loci significantly associated with POAG risk, but most of these studies were performed in populations of European-descent.MethodsTo identify population-specific and trans-population genetic associations for POAG, we genotyped 11,521 African Americans using the Illumina Metabochip as part of the Epidemiologic Architecture for Genes Linked to Environment (EAGLE) study accessing BioVU, the Vanderbilt University Medical Center’s biorepository linked to de-identified electronic health records. Among this study population, we identified 138 cases of POAG and 1376 controls and performed Metabochip-wide tests of association. We also estimated local genetic ancestry at CDKN2B-AS1, a POAG-associated locus established in European-descent populations.ResultsOverall, we did not identify significant single SNP-POAG associations after adjusting for multiple testing. We did, however, detect a significant association between POAG risk and local African genetic ancestry at CDKN2B-AS1, where on average cases were of 90% African descent compared with controls at 58% (p = 2 × 10− 6).ConclusionsThese data suggest that CDKN2B-AS1 is an important locus for POAG risk among African Americans, warranting further investigation to identify the variants underlying this association.Electronic supplementary materialThe online version of this article (10.1186/s12920-018-0392-4) contains supplementary material, which is available to authorized users.
Access and utilization of electronic health records with extensive medication lists and genetic profiles is rapidly advancing discoveries in pharmacogenomics. In this study, we analyzed ~116,000 variants on the Illumina Metabochip for response to antihypertensive and lipid lowering medications in African American adults from BioVU, the Vanderbilt University Medical Center's biorepository linked to de-identified electronic health records. Our study population included individuals who were prescribed an antihypertensive or lipid lowering medication, and who had both pre-and post-medication blood pressure or low-density lipoprotein cholesterol (LDL-C) measurements, respectively. Among those with pre-and post-medication systolic and diastolic blood pressure measurements (n=2,268), the average change in systolic and diastolic blood pressure was -0.6 mg Hg and -0.8 mm Hg, respectively. Among those with pre-and post-medication LDL-C measurements (n=1,244), the average change in LDL-C was -26.3 mg/dL. SNPs were tested for an association with change and percent change in blood pressure or blood levels of LDL-C. After adjustment for multiple testing, we did not observe any significant associations, and we were not able to replicate previously reported associations, such as in APOE and LPA, from the literature. The present study illustrates the benefits and challenges with using electronic health records linked to biorepositories for pharmacogenomic studies.
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