The KPNA3 gene may be a susceptibility candidate for schizophrenia

The present study investigated the possible association of the KPNA3 locus in the 13q14 region with schizophrenia. We detected 7 single nucleotide polymorphisms (SNPs) on 13q14, one (rs6313) present at the HTR2A locus and the other 6 at the KPNA3 locus, among 124 British family trios consisting of mother, father and affected offspring with schizophrenia. The transmission disequilibrium test (TDT) showed allelic association for rs3736830 (chi(2)=8.66, P=0.003), rs2181185 (chi(2)=3.86, P=0.049) and rs626716 (chi(2)=5.82, P=0.016), but not for rs6313 (chi(2)=0.009, P=0.926). The global P-value was 0.029 for 1000 permutations with the TDT. The 2-SNP haplotype analysis showed a disease association for the rs2273816-rs3736830 haplotypes (chi(2)=7.63, d.f.=2, P=0.022), the rs3736830-rs2181185 haplotypes (chi(2)=10.30, d.f.=2, P=0.006) and the rs2181185-rs3782929 haplotypes (chi(2)=9.26, d.f.=2, P=0.01). The global P-value was 0.034 for 1000 permutations with the 2-SNP haplotype analysis. The 6-SNP haplotype system also showed a weak association with the illness (chi(2)=15.62, d.f.=8, P=0.048), although the 1-d.f. test did not show the association for nine individual haplotypes when a P-value was corrected by the Bonferroni corrections. The present study suggests that the KPNA3 may contribute genetically to schizophrenia in a small effect size.