A genome-wide association between foveal thickness and arrhythmia.

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^-13). PheWAS identifies that the SNP was phenome-wide significantly associated with arrhythmia (β = -0.049, SE = 0.012, P = 2.50 × 10^-5). 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.