BACKGROUND

The fovea is one of the most crucial parts of the visual system and has a special structure. We aimed to identify susceptibility single nucleotide polymorphisms (SNPs) for foveal thickness in a large Japanese cohort.

METHODS

Genome-wide association study (GWAS) and replication studies were conducted in 9850 individuals from the Nagahama Study (from 2013 to 2016) and 935 individuals from the Hisayama Study. Genome-wide quantitative trait loci analyses and phenome-wide association study (PheWAS) were conducted using Biobank Japan Data for novel susceptibility SNPs. Finally, phenotypic associations were evaluated in the Nagahama Study.

RESULTS

Here we show that rs4903064, located in Double PHD Fingers 3 (DPF3), is genome-wide significantly associated with foveal thickness, which is confirmed by replication studies and meta-analysis (β = 2.18, standard error = 0.59, P = 2.93 × 10). PheWAS identifies that the SNP was phenome-wide significantly associated with arrhythmia (β = -0.049, SE = 0.012, P = 2.50 × 10). In the Nagahama Study, individuals with a thicker fovea have a significantly lower risk of premature atrial/ventricular contraction (odds ratio = 0.86, 95% confidence interval = 0.75 to 0.98, P-value = 0.022).

CONCLUSIONS

We identify a novel foveal thickness susceptibility gene that is also associated with arrhythmia. Individuals with premature atrial/ventricular contraction may be advised to undergo ophthalmological evaluation as necessary.