Ohyama Noriko, Matsunami Masatoshi, Imamura Minako, Yoshida Akihiro, Javed Azeem, Liu Xiaoxi, Kimura Ryosuke, Matsuda Koichi, Terao Chikashi, Maeda Shiro
Department of Advanced Genomic and Laboratory Medicine, Graduate School of Medicine, University of the Ryukyus, Nishihara, Japan.
Department of Cardiovascular Surgery, Okinawa Prefectural Nanbu Medical Center and Children's Medical Center, Haebaru, Japan.
Sci Rep. 2025 Feb 22;15(1):6494. doi: 10.1038/s41598-025-90195-w.
The Ryukyu archipelago is located southwest of the Japanese islands, and people originally from this region, the Ryukyu population, have a unique genetic background distinct from that of other populations, including people from mainland Japan. However, few genetic studies have focused on the Ryukyu population. In this study, we performed genome-wide association studies (GWAS) on the serum levels of alanine aminotransferase (ALT, n = 15,224), aspartate aminotransferase (AST, n = 15,203), and gamma-glutamyl transferase (GGT, n = 14,496) in the Ryukyu population. We found 13 loci with a genome-wide significant association (P < 5 × 10), three for ALT, four for AST, and six for GGT, including one novel locus associated with ALT: rs117595134-A in HMMR/HMMR-AS1, ß = - 0.131, standard error = 0.024, P = 4.90 × 10. Rs117595134-A is common in the Japanese population but is not observed in other ethnic populations in the 1000 genomes database. Additionally, 77 of 80 loci derived from Korean GWAS and 541 of 716 loci from European GWAS showed the same directions of effect (P = 1.41 × 10, P = 2.50 × 10, binomial test), indicating that most of susceptibility loci are shared between the Ryukyu population and other ethnic populations.
琉球群岛位于日本岛屿的西南部，该地区的原住民琉球人群拥有独特的遗传背景，与包括日本本土人群在内的其他人群不同。然而，很少有基因研究关注琉球人群。在本研究中，我们对琉球人群中丙氨酸氨基转移酶（ALT，n = 15224）、天冬氨酸氨基转移酶（AST，n = 15203）和γ-谷氨酰转移酶（GGT，n = 14496）的血清水平进行了全基因组关联研究（GWAS）。我们发现了13个全基因组显著关联位点（P < 5×10），其中3个与ALT相关，4个与AST相关，6个与GGT相关，包括一个与ALT相关的新位点：HMMR/HMMR-AS1中的rs117595134 - A，β = -0.131，标准误 = 0.024，P = 4.90×10。Rs117595134 - A在日本人群中常见，但在千人基因组数据库的其他种族人群中未观察到。此外，来自韩国GWAS的80个位点中的77个以及来自欧洲GWAS的716个位点中的541个显示出相同的效应方向（P = 1.41×10，P = 2.50×10，二项式检验），这表明大多数易感位点在琉球人群和其他种族人群之间是共享的。
