Nakao Shin-Ya, Miyake Masahiro, Fujiwara Kohta, Nakano Eri, Mori Yuki, Morino Kazuya, Hosoda Yoshikatsu, Tabara Yasuharu, Akiyama Masato, Yamashiro Kenji, Tamura Hiroshi, Hata Jun, Ninomiya Toshiharu, Matsuda Fumihiko, Sonoda Koh-Hei, Tsujikawa Akitaka
Department of Ophthalmology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Commun Med (Lond). 2025 Aug 28;5(1):374. doi: 10.1038/s43856-025-01087-z.
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.
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.
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).
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.
黄斑中心凹是视觉系统中最关键的部分之一，具有特殊结构。我们旨在确定一个大型日本队列中黄斑中心凹厚度的易感性单核苷酸多态性（SNP）。
在来自长滨研究（2013年至2016年）的9850名个体和久山研究的935名个体中进行全基因组关联研究（GWAS）和重复研究。使用日本生物银行数据进行全基因组数量性状位点分析和全表型组关联研究（PheWAS）以寻找新的易感性SNP。最后，在长滨研究中评估表型关联。
我们发现位于双PHD指蛋白3（DPF3）中的rs4903064与黄斑中心凹厚度在全基因组范围内显著相关，这一点在重复研究和荟萃分析中得到证实（β = 2.18，标准误 = 0.59，P = 2.93×10）。PheWAS确定该SNP与心律失常在全表型组范围内显著相关（β = -0.049，标准误 = 0.012，P = 2.50×10）。在长滨研究中，黄斑中心凹较厚的个体发生房性/室性早搏的风险显著较低（比值比 = 0.86，95%置信区间 = 0.75至0.98，P值 = 0.022）。
我们鉴定出一个与心律失常相关的新的黄斑中心凹厚度易感基因。建议有房性/室性早搏的个体在必要时接受眼科评估。
