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Genome-wide association study and meta-analysis of intraocular pressure |
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| Authors: | A. Bilge Ozel Sayoko E. Moroi David M. Reed Melisa Nika Caroline M. Schmidt Sara Akbari Kathleen Scott Frank Rozsa Hemant Pawar David C. Musch Paul R. Lichter Doug Gaasterland Kari Branham Jesse Gilbert Sarah J. Garnai Wei Chen Mohammad Othman John Heckenlively Anand Swaroop Gonçalo Abecasis David S. Friedman Don Zack Allison Ashley-Koch Megan Ulmer Jae H. Kang Yutao Liu Brian L. Yaspan Jonathan Haines R. Rand Allingham Michael A. Hauser Louis Pasquale Janey Wiggs Julia E. Richards Jun Z. Li |
| Affiliation: | 1. Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA 2. Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, USA 3. Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA 4. Eye Doctors of Washington DC, Washington, DC, USA 5. Division of Pulmonary Medicine, Allergy and Immunology, Children’s Hospital of Pittsburgh, University of Pittsburgh Medical School, Pittsburgh, PA, USA 6. Departments of Biostatistics and Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA 7. National Eye Institute, National Institutes of Health, Bethesda, MD, USA 8. Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA 9. Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA 10. Center for Human Genetics, Duke University School of Medicine, Durham, NC, USA 11. Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, MA, USA 12. Center for Human Genetics Research, Vanderbilt University School of Medicine, Nashville, TN, USA 13. Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA, USA |
| Abstract: | Elevated intraocular pressure (IOP) is a major risk factor for glaucoma and is influenced by genetic and environmental factors. Recent genome-wide association studies (GWAS) reported associations with IOP at TMCO1 and GAS7, and with primary open-angle glaucoma (POAG) at CDKN2B-AS1, CAV1/CAV2, and SIX1/SIX6. To identify novel genetic variants and replicate the published findings, we performed GWAS and meta-analysis of IOP in >6,000 subjects of European ancestry collected in three datasets: the NEI Glaucoma Human genetics collaBORation, GLAUcoma Genes and ENvironment study, and a subset of the Age-related Macular Degeneration-Michigan, Mayo, AREDS and Pennsylvania study. While no signal achieved genome-wide significance in individual datasets, a meta-analysis identified significant associations with IOP at TMCO1 (rs7518099-G, p = 8.0 × 10?8). Focused analyses of five loci previously reported for IOP and/or POAG, i.e., TMCO1, CDKN2B-AS1, GAS7, CAV1/CAV2, and SIX1/SIX6, revealed associations with IOP that were largely consistent across our three datasets, and replicated the previously reported associations in both effect size and direction. These results confirm the involvement of common variants in multiple genomic regions in regulating IOP and/or glaucoma risk. |
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