BACKGROUND: DTNBP1 is associated with schizophrenia in many studies, but the associated alleles and haplotypes vary between samples. METHOD: We assessed nine single nucleotide polymorphisms (SNPs) in this gene for association with schizophrenia in a new sample of 1021 cases and 626 controls from Ireland. RESULTS: Four SNPs give evidence of association (0.000018<p<0.045), most strongly with the common allele at rs760761. A haplotype of the common alleles of five markers (including rs760761) and the minor allele of rs2619538 overlapping the 5' end of the DTNBP1 gene also gives evidence for association (p=0.0002). Secondary analyses showed no difference in the association signal based on sex or family history. These results are in agreement with the most consistently observed association with common alleles and common-allele haplotypes, reported in a previous study of Irish cases and controls but not in an Irish high-density family sample. Our results do not support the prior report from a Swedish sample of increased association in cases with a family history of psychotic illness. Comparison of human, chimpanzee and rhesus sequence suggest that rs760761 is a particularly variable position in the primate lineage. CONCLUSION: This study provides further evidence from a large case/control sample for association of common DTNBP1 alleles and haplotypes with schizophrenia.
BACKGROUND:DTNBP1 is associated with schizophrenia in many studies, but the associated alleles and haplotypes vary between samples. METHOD: We assessed nine single nucleotide polymorphisms (SNPs) in this gene for association with schizophrenia in a new sample of 1021 cases and 626 controls from Ireland. RESULTS: Four SNPs give evidence of association (0.000018<p<0.045), most strongly with the common allele at rs760761. A haplotype of the common alleles of five markers (including rs760761) and the minor allele of rs2619538 overlapping the 5' end of the DTNBP1 gene also gives evidence for association (p=0.0002). Secondary analyses showed no difference in the association signal based on sex or family history. These results are in agreement with the most consistently observed association with common alleles and common-allele haplotypes, reported in a previous study of Irish cases and controls but not in an Irish high-density family sample. Our results do not support the prior report from a Swedish sample of increased association in cases with a family history of psychotic illness. Comparison of human, chimpanzee and rhesus sequence suggest that rs760761 is a particularly variable position in the primate lineage. CONCLUSION: This study provides further evidence from a large case/control sample for association of common DTNBP1 alleles and haplotypes with schizophrenia.
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