Common Sequence Variants in the LOXL1 Gene Confer Susceptibility to Exfoliation Glaucoma
Abstract
Glaucoma is a leading cause of irreversible blindness. A genome-wide search yielded multiple single-nucleotide polymorphisms (SNPs) in the 15q24.1 region associated with glaucoma. Further investigation revealed that the association is confined to exfoliation glaucoma (XFG). Two nonsynonymous SNPs in exon 1 of the gene LOXL1 explain the association, and the data suggest that they confer risk of XFG mainly through exfoliation syndrome (XFS). About 25% of the general population is homozygous for the highest-risk haplotype, and their risk of suffering from XFG is more than 100 times that of individuals carrying only low-risk haplotypes. The population-attributable risk is more than 99%. The product of LOXL1 catalyzes the formation of elastin fibers found to be a major component of the lesions in XFG.
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Effect sizes for common variants are typically modest; in the vast majority of cases, estimated effects are increases in risk by a factor of 1.1 to 1.5 per associated allele, with a few exceptions of ≥2 (APOE4, CFH, LOXL1).
“2) Effect sizes for common variants are typically modest. In a few cases, common variants with effects of a factor of ≥2 per allele have been found: APOE4 in Alzheimer’s disease (23), CFH in age-related macular degeneration (77–79), and LOXL1 in exfoliative glaucoma (80). In the vast majority of cases, however, the estimated effects are much smaller—mostly increases in risk by a factor of 1.1 to 1”
From Genetic Mapping in Human Disease (2008) · cites this paper as [80]
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- Authors
- Thorleifsson, G., Magnusson, K. P., Sulem, P., Walters, G. B., Gudbjartsson, D. F., Stefansson, H., Jonsson, T., Jonasdottir, A., Jonasdottir, A., Stefansdottir, G., Masson, G., Hardarson, G. A., Petursson, H., Arnarsson, A., Motallebipour, M., Wallerman, O., Wadelius, C., Gulcher, J. R., Thorsteinsdottir, U., Kong, A., Jonasson, F., & Stefansson, K.
- Affiliations
- deCODE genetics Inc, 101 Reykjavik, Iceland.
- Uppsala University (SE)
- Corresponding author
- Sulem, Patrick
- ORCID
- Venue
- Science
- Published
- 2007-09-07
- Volume
- 317
- Issue
- 5843
- Pages
- 1397-1400
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2018412721
- Cited by
- 677
- References
- 19
- Citations by year
- 2026: 10 · 2025: 17 · 2024: 42 · 2023: 31 · 2022: 34 · 2021: 33 · 2020: 32 · 2019: 26 · 2018: 39 · 2017: 27 · 2016: 24 · 2015: 35 · 2014: 48 · 2013: 39 · 2012: 33
- FWCI
- 55.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Hirsla (Landspítali University Hospital) (submittedVersion)
- Topics
- Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Ocular Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- pseudoexfoliation glaucoma, LOXL1, single nucleotide polymorphisms, genetic susceptibility, pseudoexfoliation syndrome, haplotype association, non-synonymous mutations, elastin fibers, population attributable risk
- MeSH terms
- Adipose Tissue, Amino Acid Oxidoreductases, Female, Genotype, Glaucoma, Glaucoma, Open-Angle, Humans, Iceland, Male, Gene Expression, Chi-Square Distribution, Case-Control Studies, Exfoliation Syndrome, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide
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