Statistical analysis of the associations between polymorphisms within aldehyde dehydrogenase 2 (ALDH2), and quantitative and qualitative traits extracted from a large-scale database of Japanese single-nucleotide polymorphisms (SNPs).

A scan of 4,190 single-nucleotide polymorphisms (SNPs) in 199 different genes using 38 different quantitative traits to search for associations between genotypes and phenotypes detected an association between the genotypes at rs671 of ALDH2 and gamma-glutamyltranspeptidase (gamma-GTP) levels. We examined the associations between five factors such as gender, age, rs671 genotype, alcohol-drinking habit, and serum gamma-GTP level and found that all pairs were associated except for the pair of rs671 genotype and gender and rs671 genotype and age. We further analyzed the data by both multiple regression and subgroup analyses and found that the associations between rs671 genotype and alcohol-drinking habit, alcohol-drinking habit and gamma-GTP level, gender and gamma-GTP, and age and gamma-GTP were independent of other factors. Conversely, the association between rs671 genotype and gamma-GTP level was dependent on alcohol-drinking habit. Associations between genetic and environmental factors will become a focus of medical and biological studies. Our study has shown that (1) a large sample size combined with a replication study is necessary to overcome the multiple-comparison problem, and (2) subgroup analysis along with logistic and linear multiple regression analysis may be useful to dissect a complicated relationship.