A multi-cohort genome-wide association study in African ancestry individuals reveals risk loci for primary open-angle glaucoma

A multi-cohort genome-wide association study in African ancestry individuals reveals risk loci for primary open-angle glaucoma

Cell

10.1016/j.cell.2023.12.006

https://doi.org/10.1016/j.cell.2023.12.006

Shefali S. Verma, Harini V. Gudiseva, Venkata R.M. Chavali, Rebecca J. Salowe, Yuki Bradford, Lindsay Guare, Anastasia Lucas, David W. Collins, Vrathasha Vrathasha, Rohini M. Nair, Sonika Rathi, Bingxin Zhao, Jie He, Roy Lee, Selam Zenebe-Gete, Anita S. Bowman, Caitlin P. McHugh, Michael C. Zody, Maxwell Pistilli, Naira Khachatryan, Ebenezer Daniel, Windell Murphy, Jeffrey Henderer, Tyler G. Kinzy, Sudha K. Iyengar, Neal S. Peachey, Kent D. Taylor, Xiuqing Guo, Yii-Der Ida Chen, Linda Zangwill, Christopher Girkin, Radha Ayyagari, Jeffrey Liebmann, Chimd M. Chuka-Okosa, Susan E. Williams, Stephen Akafo, Donald L. Budenz, Olusola O. Olawoye, Michele Ramsay, Adeyinka Ashaye, Onoja M. Akpa, Tin Aung, Janey L. Wiggs, Ahmara G. Ross, Qi N. Cui, Victoria Addis, Amanda Lehman, Eydie Miller-Ellis, Prithvi S. Sankar, Scott M. Williams, Gui-shuang Ying, Jessica Cooke Bailey, Jerome I. Rotter, Robert Weinreb, Chiea Chuen Khor, Michael A. Hauser, Marylyn D. Ritchie, Joan M. O’Brien

18 January 2024

Verma, S. S., Gudiseva, H. V., Chavali, V. R. M., Salowe, R. J., Bradford, Y., Guare, L., Lucas, A., Collins, D. W., Vrathasha, V., Nair, R. M., Rathi, S., Zhao, B., He, J., Lee, R., Zenebe-Gete, S., Bowman, A. S., McHugh, C. P., Zody, M. C., Pistilli, M., … O’Brien, J. M. (2024). A multi-cohort genome-wide association study in African ancestry individuals reveals risk loci for primary open-angle glaucoma. Cell, 187(2), 464-480.e10. https://doi.org/10.1016/j.cell.2023.12.006

Primary open-angle glaucoma (POAG), the leading cause of irreversible blindness worldwide, disproportionately affects individuals of African ancestry. We conducted a genome-wide association study (GWAS) for POAG in 11,275 individuals of African ancestry (6,003 cases; 5,272 controls). We detected 46 risk loci associated with POAG at genome-wide significance. Replication and post-GWAS analyses, including functionally informed fine-mapping, multiple trait co-localization, and in silico validation, implicated two previously undescribed variants (rs1666698 mapping to DBF4P2; rs34957764 mapping to ROCK1P1) and one previously associated variant (rs11824032 mapping to ARHGEF12) as likely causal. For individuals of African ancestry, a polygenic risk score (PRS) for POAG from our mega-analysis (African ancestry individuals) outperformed a PRS from summary statistics of a much larger GWAS derived from European ancestry individuals. This study quantifies the genetic architecture similarities and differences between African and non-African ancestry populations for this blinding disease.

Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)

There was no specific funding for the research done

https://oar.a-star.edu.sg/communities-collections/articles/22595

0092-8674

Genome Institute of Singapore