Genome-wide association study and meta-analysis of intraocular pressure

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 AbecasisDavid 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

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)41-57
Number of pages17
JournalHuman Genetics
Volume133
Issue number1
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

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Genome-Wide Association Study
Intraocular Pressure
Meta-Analysis
Glaucoma
Medical Genetics
Macular Degeneration
Genome
Genes
Datasets

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Ozel, A. B., Moroi, S. E., Reed, D. M., Nika, M., Schmidt, C. M., Akbari, S., ... Li, J. Z. (2014). Genome-wide association study and meta-analysis of intraocular pressure. Human Genetics, 133(1), 41-57. https://doi.org/10.1007/s00439-013-1349-5

Genome-wide association study and meta-analysis of intraocular pressure. / Ozel, A. Bilge; Moroi, Sayoko E.; Reed, David M.; Nika, Melisa; Schmidt, Caroline M.; Akbari, Sara; Scott, Kathleen; Rozsa, Frank; Pawar, Hemant; Musch, David C.; Lichter, Paul R.; Gaasterland, Doug; Branham, Kari; Gilbert, Jesse; Garnai, Sarah J.; Chen, Wei; Othman, Mohammad; Heckenlively, John; Swaroop, Anand; Abecasis, Gonçalo; Friedman, David S.; Zack, Don; Ashley-Koch, Allison; Ulmer, Megan; Kang, Jae H.; Liu, Yutao; Yaspan, Brian L.; Haines, Jonathan; Allingham, R. Rand; Hauser, Michael A.; Pasquale, Louis; Wiggs, Janey; Richards, Julia E.; Li, Jun Z.

In: Human Genetics, Vol. 133, No. 1, 01.01.2014, p. 41-57.

Research output: Contribution to journalArticle

Ozel, AB, Moroi, SE, Reed, DM, Nika, M, Schmidt, CM, Akbari, S, Scott, K, Rozsa, F, Pawar, H, Musch, DC, Lichter, PR, Gaasterland, D, Branham, K, Gilbert, J, Garnai, SJ, Chen, W, Othman, M, Heckenlively, J, Swaroop, A, Abecasis, G, Friedman, DS, Zack, D, Ashley-Koch, A, Ulmer, M, Kang, JH, Liu, Y, Yaspan, BL, Haines, J, Allingham, RR, Hauser, MA, Pasquale, L, Wiggs, J, Richards, JE & Li, JZ 2014, 'Genome-wide association study and meta-analysis of intraocular pressure', Human Genetics, vol. 133, no. 1, pp. 41-57. https://doi.org/10.1007/s00439-013-1349-5
Ozel AB, Moroi SE, Reed DM, Nika M, Schmidt CM, Akbari S et al. Genome-wide association study and meta-analysis of intraocular pressure. Human Genetics. 2014 Jan 1;133(1):41-57. https://doi.org/10.1007/s00439-013-1349-5
Ozel, A. Bilge ; Moroi, Sayoko E. ; Reed, David M. ; Nika, Melisa ; Schmidt, Caroline M. ; Akbari, Sara ; Scott, Kathleen ; Rozsa, Frank ; Pawar, Hemant ; Musch, David C. ; Lichter, Paul R. ; Gaasterland, Doug ; Branham, Kari ; Gilbert, Jesse ; Garnai, Sarah J. ; Chen, Wei ; Othman, Mohammad ; Heckenlively, John ; Swaroop, Anand ; Abecasis, Gonçalo ; Friedman, David S. ; Zack, Don ; Ashley-Koch, Allison ; Ulmer, Megan ; Kang, Jae H. ; Liu, Yutao ; Yaspan, Brian L. ; Haines, Jonathan ; Allingham, R. Rand ; Hauser, Michael A. ; Pasquale, Louis ; Wiggs, Janey ; Richards, Julia E. ; Li, Jun Z. / Genome-wide association study and meta-analysis of intraocular pressure. In: Human Genetics. 2014 ; Vol. 133, No. 1. pp. 41-57.
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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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AU - Ozel, A. Bilge

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AU - Reed, David M.

AU - Nika, Melisa

AU - Schmidt, Caroline M.

AU - Akbari, Sara

AU - Scott, Kathleen

AU - Rozsa, Frank

AU - Pawar, Hemant

AU - Musch, David C.

AU - Lichter, Paul R.

AU - Gaasterland, Doug

AU - Branham, Kari

AU - Gilbert, Jesse

AU - Garnai, Sarah J.

AU - Chen, Wei

AU - Othman, Mohammad

AU - Heckenlively, John

AU - Swaroop, Anand

AU - Abecasis, Gonçalo

AU - Friedman, David S.

AU - Zack, Don

AU - Ashley-Koch, Allison

AU - Ulmer, Megan

AU - Kang, Jae H.

AU - Liu, Yutao

AU - Yaspan, Brian L.

AU - Haines, Jonathan

AU - Allingham, R. Rand

AU - Hauser, Michael A.

AU - Pasquale, Louis

AU - Wiggs, Janey

AU - Richards, Julia E.

AU - Li, Jun Z.

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