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Novel ancestry-specific primary open-angle glaucoma loci and shared biology with vascular mechanisms and cell proliferation.
- Source :
-
Cell reports. Medicine [Cell Rep Med] 2024 Feb 20; Vol. 5 (2), pp. 101430. - Publication Year :
- 2024
-
Abstract
- Primary open-angle glaucoma (POAG), a leading cause of irreversible blindness globally, shows disparity in prevalence and manifestations across ancestries. We perform meta-analysis across 15 biobanks (of the Global Biobank Meta-analysis Initiative) (n = 1,487,441: cases = 26,848) and merge with previous multi-ancestry studies, with the combined dataset representing the largest and most diverse POAG study to date (n = 1,478,037: cases = 46,325) and identify 17 novel significant loci, 5 of which were ancestry specific. Gene-enrichment and transcriptome-wide association analyses implicate vascular and cancer genes, a fifth of which are primary ciliary related. We perform an extensive statistical analysis of SIX6 and CDKN2B-AS1 loci in human GTEx data and across large electronic health records showing interaction between SIX6 gene and causal variants in the chr9p21.3 locus, with expression effect on CDKN2A/B. Our results suggest that some POAG risk variants may be ancestry specific, sex specific, or both, and support the contribution of genes involved in programmed cell death in POAG pathogenesis.<br />Competing Interests: Declaration of interests E.R.G. received an honorarium from the journal Circulation Research of the American Heart Association as a member of the Editorial Board. S.M. is a co-founder and holds stock in Seonix Pty Ltd.<br /> (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 2666-3791
- Volume :
- 5
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cell reports. Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 38382466
- Full Text :
- https://doi.org/10.1016/j.xcrm.2024.101430