A family- and population-based study of the UFD1L gene for schizophrenia.

The present work was undertaken to investigate the association of the UFD1L locus with schizophrenia among 304 Chinese family trios of Han descent. We detected four single nucleotide polymorphisms (SNPs) in the 5'-end region of the UFD1L gene. The transmission disequilibrium test (TDT) revealed allelic associations for rs5746744 (chi(2) = 8.02, P = 0.005) and rs1547931 (chi(2) = 7.18, P = 0.007), but failed to replicate disease association for rs5992403 present in the promoter region, which was initially found in Italian and Canadian samples. The allelic association for rs5746744 and rs1547931 was replicated with independently recruited case-control samples. The 2-SNP haplotype analysis showed an association for the rs5992403-rs5746744 haplotypes (chi(2) = 18.92, df = 3, P = 0.0003), the rs5746744-rs1547931 haplotypes (chi(2) = 11.06, df = 3, P = 0.011) and the rs1547931-rs2238769 haplotypes (chi(2) = 18.88, df = 3, P = 0.0003). The 4-SNP haplotype analysis also showed strong association with illness (chi(2) = 29.54, df = 9, P = 0.0005) but there were more than one individual haplotypes with a low frequency excessively non-transmitted. The four SNPs tested were not located in the same LD block among the Chinese population. This study raises the possibility that a disease-resistant variant may be carried by two or more haplotypes at the UFD1L locus due to frequent recombination during meiosis.