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

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