Rs3825942

From SNPedia

rs3825942, also known as G153D, a SNP causing an amino acid change in the lysyl oxidase 1 LOXL1 gene, has been linked to exfoliation glaucoma (also known as exfoliation syndrome). This form of glaucoma causes up to 10% of the cases of blindness in many countries, including the US. [PMID 17690259] From the abstract of this study: "Approximately 25% of the general population is homozygous for the highest risk haplotype and their risk of suffering XFG (exfoliation glaucoma) is over 100 times that of those only carrying low-risk haplotypes."

The risk allele for this SNP is rs3825942(C), as oriented with respect to the dbSNP entry, and it confers a estimated relative risk (by itself) of 27 compared to the (T) allele. The odds ratio is 20.10 (CI 10.80-37.41). [Note that the (C) allele is actually quite common in most European populations.]

A meta-analysis including 24 articles across 5 ethnicities (Caucasian, African, Japanese, Indian, and Chinese) concluded that rs3825942 is the common disease-associated SNP in all populations, whereas rs1048661 and rs2165241 were inconsistent. The odds ratio is approximately 10 for rs3825942(C;C), while the heterozygote rs3825942(C;T) was not statistically significant. rs3825942 was not associated with primary open angle glaucoma (POAG).[PMID 20142848]

With so many people at high risk, shouldn't the number of cases be much higher? Not necessarily, since glaucoma risk only becomes high in older individuals. [To put it another way: plenty of folks don't live long enough to find out if they would have gotten glaucoma.] The estimate for glaucoma incidence worldwide is 10-20% only for individuals over 60 years of age; in Iceland, where glaucoma incidence is high, 40% of individuals 80 or older show signs of exfoliation syndrome, which has been seen to convert to exfolation glaucoma at a rate of 60% - over a 15 year period. [PMID 12928689, PMID 10463402, PMID 17224761]

discussed in this blog post

[PMID 18385788] rs1048661 (G), rs3825942 (G), and rs2165241 (T) are highly associated with XFS and XFG in American and European populations. The GGT haplotype constitutes a major risk haplotype for exfoliation.

[PMID 18385063] Confirmed as risk for pseudoexfoliation (PEX) and pseudoexfoliation glaucoma (PEXG) in populations of German and Italian descent.

GWAS
SNP	rs3825942
PubMedID	[PMID 17690259]
Condition	Exfoliation glaucoma
Gene	LOXL1
Risk Allele	G
pValue	3.00E-021
OR	20.1
95% CI	10.80-37.41

[PMID 19503743] Association of LOXL1 polymorphisms with pseudoexfoliation in the Chinese

[PMID 19936304] Evaluation of LOXL1 polymorphisms in exfoliation syndrome in a Chinese population