Here we perform GWAS and a two-staged replication study of serum AAT levels using 9,359 Japanese healthy individuals participating in the Nagahama Study and show a total of three missense variants, rs671, rs1169288 and rs1260326 in metabolic syndrome-related genes, ALDH2, HNF1A and GCKR, respectively. This evidence concerns the gene ALDH2 and metabolic syndrome.