서강대학교

초록/요약

Most common diseases including schizophrenia, diabetes, and cancer, are complex genetic traits, with multiple genetic and environmental factors contributing to disease susceptibility. It has been proposed that SNPs, which occurr in 0.1% of human genome, influence susceptibility to common disease. Many studies have been conducted, ranging from candidate gene research to genome wide association studies (GWAS), to identify genetics factors associated with complex diseases. Genetic association studies with schizophrenia, acute myeloid leukemia (AML), and Hirschsprung disease (HSCR) were conducted. These diseases are regarded as a multifactorial and polygenic disorder. First, the genome-wide association and follow-up study for schizophrenia was performed in Korean cohorts with the Illumina HumanOmni1-Quad V1.0 Microarray. In a genome-wide study, I identified the lowest P-value in MECR gene. In subsequent fine-mapping analysis, the MECR rs12738007 was replicated. The identification of putative schizophrenia susceptibility loci could provide new insights into genetic factors related with schizophrenia and clues for the development of diagnosis strategies. Second, sixteen variants of CDA were analyzed among 50 normal karyotype AML (NK-AML) patients, 45 abnormal karyotype AML (AK-AML) patients, and 241 normal controls. The rs2072671 showed a significant association with NK-AML. The AC and CC genotypes of rs2072671 were also correlated with clinical outcomes, shorter overall survival rates and first complete remission duration. These results indicate that rs2072671 in CDA may be an important prognostic marker in NK-AML patients. Finally, nine SNPs on IL-11 were genotyped in 187 HSCR patients and 283 controls. Several SNPs and the haplotype showed significant associations with HSCR. In analysis of HSCR subtypes, S-HSCR and L-HSCR showed significant signals at several SNPs of IL-11. Genetic variations of IL-11 may be associated with the risk of HSCR and/or the mechanisms related to ENS development. Although further replication in a larger cohort and functional evaluations are needed, these findings suggest that the association signals with schizophrenia, AML, and HSCR could be the preliminary information for the prediction, prevention, and treatment of these diseases.