한빛사논문
- 조회422
Yizhou Zhu 1, Cagdas Tazearslan 2, Michael G Rosenfeld 3,4, Andras Fiser 5,6, Yousin Suh 1,7
1Department of Obstetrics and Gynecology, Columbia University, New York, New York, USA.
2Department of Genetics, Albert Einstein College of Medicine, Bronx, New York, USA.
3Department of Medicine, School of Medicine, University of California, La Jolla, California, USA.
4Howard Hughes Medical Institute, University of California, La Jolla, California, USA.
5Department of Systems & Computational Biology, Albert Einstein College of Medicine, New York, New York, USA.
6Department of Biochemistry, Albert Einstein College of Medicine, New York, New York, USA.
7Department of Genetics and Development, Columbia University, New York, New York, USA.
Corresponding author : Yousin Suh
Abstract
Glaucoma is a leading cause of irreversible blindness, with advanced age being the single most significant risk factor. However, the mechanisms underlying the relationship between aging and glaucoma remain unclear. Genome-wide association studies (GWAS) have successfully identified genetic variants strongly associated with increased glaucoma risk. Understanding how these variants function in pathogenesis is crucial for translating genetic associations into molecular mechanisms and, ultimately, clinical applications. The chromosome 9p21.3 locus is among the most replicated glaucoma risk loci discovered by GWAS. Nonetheless, the absence of protein-coding genes in the locus makes interpreting the disease association challenging, leaving the causal variant and molecular mechanism elusive. In this study, we report the identification of a functional glaucoma risk variant, rs6475604. By employing computational and experimental methods, we demonstrated that rs6475604 resides in a repressive regulatory element. Risk allele of rs6475604 disrupts the binding of YY1, a transcription factor known to repress the expression of a neighboring gene in 9p21.3, p16INK4A, which plays a crucial role in cellular senescence and aging. These findings suggest that the glaucoma disease variant contributes to accelerated senescence, providing a molecular link between glaucoma risk and an essential cellular mechanism for human aging.
논문정보
- Research article
- 2023년 06월 (BRIC 등록일 2023-07-07)
- 국외 연구진
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