Schizophrenia is a serious neuropsychiatric illness affecting about 1% of the world’s population. It is considered a complex inheritance disorder. A number of genes are involved in combination in the etiology of the ...Schizophrenia is a serious neuropsychiatric illness affecting about 1% of the world’s population. It is considered a complex inheritance disorder. A number of genes are involved in combination in the etiology of the disorder. Evidence implicates the altered dopaminergic trans- mission in schizophrenia. In the present study, in order to identify susceptibility genes for schizophrenia in dopaminergic metabolism, we analyzed 59 single nucleotide polymorphisms (SNPs) in 24 genes of the dopaminergic pathway among 82 unrelated patients with schizophre- nia and 108 matched normal controls. Considering that traditional single-locus association stud- ies ignore the multigenic nature of complex diseases and do not take into account possible in- teractions between susceptibility genes, we proposed a multi-locus analysis method, using the posterior probability of morbidity as a measure of absolute disease risk for a multi-locus genotype combination, and developed an algorithm based on perturbation and average to detect the sus- ceptibility multi-locus genotype combinations, as well as to repress noise and avoid false positive results at our best. A three-locus SNP genotype combination involved in the interactions of COMT and ALDH3B1 genes was detected to be significantly susceptible to schizophrenia.展开更多
基金This study was supported by the National Natu-ral Science Foundation of China(Grant Nos.60234020 and 60171038)MOST project(Grant No.2001CCA01400)the National High Tech-nology Research and Development Program of China(Grant No.2001 AA221071).
文摘Schizophrenia is a serious neuropsychiatric illness affecting about 1% of the world’s population. It is considered a complex inheritance disorder. A number of genes are involved in combination in the etiology of the disorder. Evidence implicates the altered dopaminergic trans- mission in schizophrenia. In the present study, in order to identify susceptibility genes for schizophrenia in dopaminergic metabolism, we analyzed 59 single nucleotide polymorphisms (SNPs) in 24 genes of the dopaminergic pathway among 82 unrelated patients with schizophre- nia and 108 matched normal controls. Considering that traditional single-locus association stud- ies ignore the multigenic nature of complex diseases and do not take into account possible in- teractions between susceptibility genes, we proposed a multi-locus analysis method, using the posterior probability of morbidity as a measure of absolute disease risk for a multi-locus genotype combination, and developed an algorithm based on perturbation and average to detect the sus- ceptibility multi-locus genotype combinations, as well as to repress noise and avoid false positive results at our best. A three-locus SNP genotype combination involved in the interactions of COMT and ALDH3B1 genes was detected to be significantly susceptible to schizophrenia.
