Local Genetic Ancestry in CDKN2B-AS1 is Associated with Primary Open-angle Glaucoma in an African American Cohort Extracted from De-identified Electronic Health Records

Overview

Journal BMC Med Genomics

Publisher Biomed Central

Specialty Genetics

Date 2018 Sep 27

PMID 30255811

Citations 9

Authors

Nicole A Restrepo

Sarah M Laper

Eric Farber-Eger

Dana C Crawford

Affiliations

Soon will be listed here.

Abstract

Background: Glaucoma 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.

Methods: To 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.

Results: Overall, 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).

Conclusions: These 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.

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References

Yu N, Hallstrom B, Fagerberg L, Ponten F, Kawaji H, Carninci P . Complementing tissue characterization by integrating transcriptome profiling from the Human Protein Atlas and from the FANTOM5 consortium. Nucleic Acids Res. 2015; 43(14):6787-98. PMC: 4538815. DOI: 10.1093/nar/gkv608. View

Crawford D, Goodloe R, Brown-Gentry K, Wilson S, Roberson J, Gillani N . Characterization of the Metabochip in diverse populations from the International HapMap Project in the Epidemiologic Architecture for Genes Linked to Environment (EAGLE) project. Pac Symp Biocomput. 2013; :188-99. PMC: 3584704. View

Suzuki Y, Shirato S, Taniguchi F, Ohara K, Nishimaki K, Ohta S . Mutations in the TIGR gene in familial primary open-angle glaucoma in Japan. Am J Hum Genet. 1997; 61(5):1202-4. PMC: 1716051. DOI: 10.1086/301612. View

Chandrasekaran S, Cumming R, Rochtchina E, Mitchell P . Associations between elevated intraocular pressure and glaucoma, use of glaucoma medications, and 5-year incident cataract: the Blue Mountains Eye Study. Ophthalmology. 2006; 113(3):417-24. DOI: 10.1016/j.ophtha.2005.10.050. View

Ladapo J, Kymes S, Ladapo J, Nwosu V, Pasquale L . Projected clinical outcomes of glaucoma screening in African American individuals. Arch Ophthalmol. 2012; 130(3):365-72. PMC: 8075062. DOI: 10.1001/archopthalmol.2011.1224. View

Baran Y, Pasaniuc B, Sankararaman S, Torgerson D, Gignoux C, Eng C . Fast and accurate inference of local ancestry in Latino populations. Bioinformatics. 2012; 28(10):1359-67. PMC: 3348558. DOI: 10.1093/bioinformatics/bts144. View

Arjunan P, Gnanaprakasam J, Ananth S, Romej M, Rajalakshmi V, Prasad P . Increased Retinal Expression of the Pro-Angiogenic Receptor GPR91 via BMP6 in a Mouse Model of Juvenile Hemochromatosis. Invest Ophthalmol Vis Sci. 2016; 57(4):1612-9. PMC: 4824383. DOI: 10.1167/iovs.15-17437. View

Baharian S, Barakatt M, Gignoux C, Shringarpure S, Errington J, Blot W . The Great Migration and African-American Genomic Diversity. PLoS Genet. 2016; 12(5):e1006059. PMC: 4883799. DOI: 10.1371/journal.pgen.1006059. View

Gauderman W . Sample size requirements for association studies of gene-gene interaction. Am J Epidemiol. 2002; 155(5):478-84. DOI: 10.1093/aje/155.5.478. View

10.

Willer C, Sanna S, Jackson A, Scuteri A, Bonnycastle L, Clarke R . Newly identified loci that influence lipid concentrations and risk of coronary artery disease. Nat Genet. 2008; 40(2):161-9. PMC: 5206900. DOI: 10.1038/ng.76. View

11.

Osman W, Low S, Takahashi A, Kubo M, Nakamura Y . A genome-wide association study in the Japanese population confirms 9p21 and 14q23 as susceptibility loci for primary open angle glaucoma. Hum Mol Genet. 2012; 21(12):2836-42. DOI: 10.1093/hmg/dds103. View

12.

Charlesworth J, Kramer P, Dyer T, Diego V, Samples J, Craig J . The path to open-angle glaucoma gene discovery: endophenotypic status of intraocular pressure, cup-to-disc ratio, and central corneal thickness. Invest Ophthalmol Vis Sci. 2010; 51(7):3509-14. PMC: 2904007. DOI: 10.1167/iovs.09-4786. View

13.

Stein J, Kim D, Niziol L, Talwar N, Nan B, Musch D . Differences in rates of glaucoma among Asian Americans and other racial groups, and among various Asian ethnic groups. Ophthalmology. 2011; 118(6):1031-7. PMC: 3109193. DOI: 10.1016/j.ophtha.2010.10.024. View

14.

Li Z, Allingham R, Nakano M, Jia L, Chen Y, Ikeda Y . A common variant near TGFBR3 is associated with primary open angle glaucoma. Hum Mol Genet. 2015; 24(13):3880-92. PMC: 4459396. DOI: 10.1093/hmg/ddv128. View

15.

Crawford D, Goodloe R, Farber-Eger E, Boston J, Pendergrass S, Haines J . Leveraging Epidemiologic and Clinical Collections for Genomic Studies of Complex Traits. Hum Hered. 2015; 79(3-4):137-46. PMC: 4528966. DOI: 10.1159/000381805. View

16.

Jiang X, Varma R, Wu S, Torres M, Azen S, Francis B . Baseline risk factors that predict the development of open-angle glaucoma in a population: the Los Angeles Latino Eye Study. Ophthalmology. 2012; 119(11):2245-53. PMC: 3474872. DOI: 10.1016/j.ophtha.2012.05.030. View

17.

Johnson A, Handsaker R, Pulit S, Nizzari M, ODonnell C, de Bakker P . SNAP: a web-based tool for identification and annotation of proxy SNPs using HapMap. Bioinformatics. 2008; 24(24):2938-9. PMC: 2720775. DOI: 10.1093/bioinformatics/btn564. View

18.

Congdon N, OColmain B, Klaver C, Klein R, Munoz B, Friedman D . Causes and prevalence of visual impairment among adults in the United States. Arch Ophthalmol. 2004; 122(4):477-85. DOI: 10.1001/archopht.122.4.477. View

19.

Pulley J, Clayton E, Bernard G, Roden D, Masys D . Principles of human subjects protections applied in an opt-out, de-identified biobank. Clin Transl Sci. 2010; 3(1):42-8. PMC: 3075971. DOI: 10.1111/j.1752-8062.2010.00175.x. View

20.

Stone E, Fingert J, Alward W, Nguyen T, Polansky J, Sunden S . Identification of a gene that causes primary open angle glaucoma. Science. 1997; 275(5300):668-70. DOI: 10.1126/science.275.5300.668. View