A variant in HMMR/HMMR-AS1 is associated with serum alanine aminotransferase levels in the Ryukyu population

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<sup>-8</sup>), 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<sup>-8</sup>. 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<sup>-19</sup>, P = 2.50 × 10<sup>-44</sup>, binomial test), indicating that most of susceptibility loci are shared between the Ryukyu population and other ethnic populations.

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Publication Details

Journal
Scientific Reports
Published
2025-02-22
DOI
https://doi.org/10.1038/s41598-025-90195-w
Primary Topic
Liver Disease Diagnosis and Treatment
Type
article
Field-Weighted Citation Impact
0.00

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article

A variant in HMMR/HMMR-AS1 is associated with serum alanine aminotransferase levels in the Ryukyu population

Kaori Muto, Chikashi C. Terao, Yuji Yamanashi, Yu‐ki Iwasaki et al.
Scientific Reports
Liver Disease Diagnosis and Treatment
article

A variant in HMMR/HMMR-AS1 is associated with serum alanine aminotransferase levels in the Ryukyu population

Kaori Muto, Chikashi C. Terao, Yuji Yamanashi, Yu‐ki Iwasaki, Yasunobu Nagata, Shuzo Kobayashi, Natsuhiko Kumasaka, Shigeo Murayama, Kozo Yoshimori, Ryosuke Kimura, Yoichiro Kamatani, Nagaaki Ohyama, Yukinori Okada, Wataru Obara, Yoji Sagiya, Yasuo Takahashi, Yusuke Furukawa, Hiroki Yamaguchi, Minako Imamura, Takayuki Morisaki, Masatoshi Matsunami, Daisuke Obata, Akiko Nagai, Koichi Matsuda, Chikako Nito, Masahiko Higashiyama, Yoshinori Murakami, Satoshi Wakita, Kazuhisa Takahashi, Xiaoxi Liu, Yukihiro Koretsune, Satoshi Asai, Shiro Maeda, Akihiro Yoshida, Yusuke Nakamura, Yoshio Miki, Yoshinobu Koga, Anum Javed, Ken Yamaji, Akihide Masumoto, Shinichi Higashiue
article en

Abstract

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<sup>-8</sup>), 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<sup>-8</sup>. 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<sup>-19</sup>, P = 2.50 × 10<sup>-44</sup>, binomial test), indicating that most of susceptibility loci are shared between the Ryukyu population and other ethnic populations.

Scientific ReportsVol. 15(1)
Nihon University (JP), University of Shizuoka (JP), Shiga University of Medical Science (JP), Iwate Medical University (JP), University of the Ryukyus (JP), Juntendo University (JP), Osaka National Hospital (JP), Fukuoka Tokushukai Hospital (JP), Japan Anti Tuberculosis Association (JP), Okinawa Prefectural Chubu Hospital (JP), Shizuoka General Hospital (JP), The Cancer Institute Hospital (JP), Aso Iizuka Hospital (JP), Gunma Children's Medical Center (JP), RIKEN Center for Integrative Medical Sciences (JP), Osaka International Cancer Institute (JP), Tokyo Metropolitan Geriatric Hospital (JP), Fukujuji Hospital (JP), University of the Ryukyus University Hospital (JP), Hokuto Hospital (JP), Japanese Foundation For Cancer Research (JP), The University of Tokyo (JP), Nippon Medical School (JP)
University of the Ryukyus
Openalex Percentile: Top 95%
Liver Disease Diagnosis and Treatment
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