The SNP rs7341475 was successfully genotyped in totaling 2176 individuals and the genotype frequencies were in Hardy-Weinberg equilibrium. The distribution of genotypes and alleles of rs7341475 is shown in the . As predicted, we observed a consistent and significant (one tail p=0.0475) difference in case versus control allele frequencies only in AJ women with an Odds Ratio of 1.23.
Genotype and Allele Frequencies of the SNP rs7341475 of RELN Gene in Cases and Controls
When we subtracted the SZA individuals from our cases and repeated the analysis, we observed the same trend but with reduced statistical significance (one tail p=0.065, data not shown) again in AJ females only. We conclude that the SZA patients contribute to the association and excluding them reduces the sample size and, consequently, the statistical power. This result is consistent with the result published later by the same group (Pisante et al. 2009
For our QTL analysis with the 9 factors from the McGrath et al factor analysis (McGrath et al. 2009
) , as shown in the , two factors (CHA, HAL) show nominal association with rs7341475 with the best signal (p=0.018) in male-allelic analysis for factor CHA and the second best signal (p=0.035) in female-genotypic analysis for factor HAL. In both cases, the G allele is nominally associated with higher scores (i.e., more symptoms). However, these results do not withstand multiple test correction and we include them only to suggest approaches that could improve the power of future replication attempts and provide information on the complex nature of the observed associations.
Quantitative trait loci (QTL) association analysis of rs7341475 with 9 factors in AJ SZ patients
In summary, we have replicated the genetic association between a common variant in RELN
and SZ in AJ women reported by Shifman et al
. in a population of the same origin. Our results strengthen the evidence for RELN
’s involvement in SZ and provide sex specific connections of the disease-associated variant with phenotypic features of SZ. It is of interest that RELN
expression has also been shown to be sex-related in SZ patients (Eastwood, Harrison 2003
). Our data add to the accumulating evidence that implicate RELN
in SZ through sex specific mechanism(s).