A large cross-ancestry meta-analysis of genome-wide association studies identifies 69 novel risk loci for primary open-angle glaucoma and includes a genetic link with Alzheimer's disease

Gharahkhani, P.; Jorgenson, E.; Hysi, P.; Khawaja, A. P.; Pendergrass, S.; Han, X.; Ong, J. S.; Hewitt, A. W.; Segre, A.; Igo, R. P.; Choquet, H.; Qassim, A.; Josyula, N. S.; Cooke Bailey, J. N.; Bonnemaijer, P.; Iglesias, A.; Siggs, O. M.; Young, T.; Vitart, V.; Thiadens, A. A. H. J.; Karjalainen, J.; Uebe, S.; Melles, R. B.; Nair, S.; Luben, R.; Simcoe, M.; Amersinghe, N.; Cree, A. J.; Hohn, R.; Poplawski, A.; Chen, L. J.; Cheng, C.-Y.; Vithana, E. N.; NEIGHBORHOOD consortium,; ANZRAG consortium,; Biobank Japan project,; FinnGen study,; UK Biobank Eye and Vision Consortium,; GIGA s

doi:10.1101/2020.01.30.927822

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bioRxiv · 10.1101/2020.01.30.927822

A large cross-ancestry meta-analysis of genome-wide association studies identifies 69 novel risk loci for primary open-angle glaucoma and includes a genetic link with Alzheimer's disease

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Abstract

We conducted a large multi-ethnic meta-analysis of genome-wide association studies for primary open-angle glaucoma (POAG) on a total of 34,179 cases vs 349,321 controls, and identified 127 independent risk loci, almost doubling the number of known loci for POAG. The majority of loci have broadly consistent effect across European, Asian and African ancestries. We identify a link, both genome-wide and at specific loci, between POAG and Alzheimers disease. Gene expression data and bioinformatic functional analyses provide further support for the functional relevance of the POAG risk genes. Several drug compounds target these risk genes and may be potential candidates for developing novel POAG treatments.

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Gharahkhani, P., Jorgenson, E., Hysi, P., Khawaja, A. P., Pendergrass, S., Han, X., Ong, J. S., Hewitt, A. W., Segre, A., Igo, R. P., Choquet, H., Qassim, A., Josyula, N. S., Cooke Bailey, J. N., Bonnemaijer, P., Iglesias, A., Siggs, O. M., Young, T., Vitart, V., Thiadens, A. A. H. J., Karjalainen, J., Uebe, S., Melles, R. B., Nair, S., Luben, R., Simcoe, M., Amersinghe, N., Cree, A. J., Hohn, R., Poplawski, A., Chen, L. J., Cheng, C.-Y., Vithana, E. N., NEIGHBORHOOD consortium,, ANZRAG consortium,, Biobank Japan project,, FinnGen study,, UK Biobank Eye and Vision Consortium,, GIGA s. 2020-02-03. A large cross-ancestry meta-analysis of genome-wide association studies identifies 69 novel risk loci for primary open-angle glaucoma and includes a genetic link with Alzheimer's disease. https://doi.org/10.1101/2020.01.30.927822

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