Association of SIX1-SIX6 polymorphisms with peripapillary retinal nerve fibre layer thickness in children
Shi Yao Lu1, Xiu Juan Zhang1, Yu Meng Wang1
1Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.
Insights
Genetic variants in SIX1-SIX6 are linked to peripapillary retinal nerve fibre layer (p-RNFL) thickness in children. These associations show age-dependent and sex-specific effects, particularly in the temporal-inferior region.
Area of Science:
- Ophthalmology
- Genetics
- Pediatric Eye Research
Background:
- Previous studies linked SIX1-SIX6 variants to peripapillary retinal nerve fibre layer (p-RNFL) thickness in adults.
- The role of these genetic variants in children's p-RNFL thickness remains less understood.
Purpose of the Study:
- To investigate the association between SIX1-SIX6 variants and p-RNFL thickness in children.
- To explore these associations based on spatial location, age, and sex.
Main Methods:
- Genotyping of three single-nucleotide polymorphisms (SNPs) at the SIX1-SIX6 locus in 2878 school children (aged 6-9 years).
- Evaluation of SNP associations with global and sectoral p-RNFL thickness using multiple linear regression.
Main Results:
- SNPs rs33912345 and rs10483727 were significantly associated with thinner temporal-inferior p-RNFL thickness.
- These associations were strongest in 8-9 year olds and observed in boys but not girls.
- SNP rs12436579 showed a nominal association with thicker nasal-inferior p-RNFL thickness.
Conclusions:
- SIX1-SIX6 variants rs33912345 and rs10483727 are associated with p-RNFL thickness in children, particularly in the temporal-inferior sector.
- Age-dependent and sex-specific effects were noted for these SNPs.
- Findings suggest a role for SIX1-SIX6 in retinal nerve fibre layer variation during childhood neural development.
Purpose:
Association of SIX1-SIX6 variants with peripapillary retinal nerve fibre layer (p-RNFL) thickness had been reported in adults. This study aimed to investigate these associations in children, with further explorations by spatial, age and sex stratifications.
Methods:
2878 school children aged between 6 and 9 years were enrolled from the Hong Kong Children Eye Study. Three single-nucleotide polymorphisms (SNPs) at the SIX1-SIX6 locus were genotyped. The association of each SNP with p-RNFL thickness (including global and sectoral thickness) were evaluated using multiple linear regression.
Results:
SNPs rs33912345 (p=7.7×10-4) and rs10483727 (p=0.0013) showed significant associations with temporal-inferior p-RNFL thickness. The C allele of rs33912345 was associated with a thinner temporal-inferior p-RNFL by an average of 2.44 µm, while rs10483727-T was associated with a thinner temporal-inferior p-RNFL by 2.32 µm. The association with temporal-inferior p-RNFL was the strongest in the 8-9 year-old group for rs33912345 (p=5.2×10-4) and rs10483727 (p=3.3×10-4). Both SNPs were significantly associated with temporal-inferior p-RNFL thickness in boys (p<0.0017), but not in girls (p>0.05). In contrast, rs12436579-C (β=1.66; p=0.0059), but not rs33912345-C (β=1.31; p=0.052) or rs10483727-T (β=1.19; p=0.078), was nominally associated with a thicker nasal-inferior p-RNFL.
Conclusions:
Both rs33912345 and rs10483727 at SIX1-SIX6 were associated with p-RNFL thickness in children, especially at the temporal-inferior sector, with age-dependent and sex-specific effects. SNP rs12436579 was associated with nasal-inferior p-RNFL thickness. Our findings suggested a role of SIX1-SIX6 in RNFL variation during neural retina development in childhood.
