GWAS-by-subtraction reveals an IOP-independent component of primary open angle glaucoma

Huang, Yu; Plotnikov, Denis; Wang, Huan; Shi, Danli; Li, Cong; Zhang, Xueli; Zhang, Xiayin; Tang, Shulin; Shang, Xianwen; Hu, Yijun; Yu, Honghua; Zhang, Hongyang; Guggenheim, Jeremy A.; He, Mingguang

doi:10.1038/s41467-024-53331-0

Nat Commun

2024

DOI: 10.1038/s41467-024-53331-0

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GWAS-by-subtraction reveals an IOP-independent component of primary open angle glaucoma

Yu Huang,

Denis Plotnikov,

Huan Wang

et al.

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Candidate SNP Markers Significantly Altering the Affinity of the TATA-Binding Protein for the Promoters of Human Genes Associated with Primary Open-Angle Glaucoma

Zolotareva,

Dotsenko,

Podkolodnyy

et al. 2024

IJMS

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Primary open-angle glaucoma (POAG) is the most common form of glaucoma. This condition leads to optic nerve degeneration and eventually to blindness. Tobacco smoking, alcohol consumption, fast-food diets, obesity, heavy weight lifting, high-intensity physical exercises, and many other bad habits are lifestyle-related risk factors for POAG. By contrast, moderate-intensity aerobic exercise and the Mediterranean diet can alleviate POAG. In this work, we for the first time estimated the phylostratigraphic age indices (PAIs) of all 153 POAG-related human genes in the NCBI Gene Database. This allowed us to separate them into two groups: POAG-related genes that appeared before and after the phylum Chordata, that is, ophthalmologically speaking, before and after the camera-type eye evolved. Next, in the POAG-related genes’ promoters, we in silico predicted all 3835 candidate SNP markers that significantly change the TATA-binding protein (TBP) affinity for these promoters and, through this molecular mechanism, the expression levels of these genes. Finally, we verified our results against five independent web services—PANTHER, DAVID, STRING, MetaScape, and GeneMANIA—as well as the ClinVar database. It was concluded that POAG is likely to be a symptom of the human self-domestication syndrome, a downside of being civilized.

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Candidate SNP Markers Significantly Altering the Affinity of the TATA-Binding Protein for the Promoters of Human Genes Associated with Primary Open-Angle Glaucoma

Zolotareva,

Dotsenko,

Podkolodnyy

et al. 2024

IJMS

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GWAS-by-subtraction reveals an IOP-independent component of primary open angle glaucoma

Cited by 1 publication

References 83 publications

Candidate SNP Markers Significantly Altering the Affinity of the TATA-Binding Protein for the Promoters of Human Genes Associated with Primary Open-Angle Glaucoma

Candidate SNP Markers Significantly Altering the Affinity of the TATA-Binding Protein for the Promoters of Human Genes Associated with Primary Open-Angle Glaucoma

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