Supplementary Material for: Genetic Association of TCF4 and AKT1 Gene Variants with the Age at Onset of Schizophrenia

<b><i>Background:</i></b> Age at onset (AAO) is a known prognostic indicator for schizophrenia and is hypothesized to correlate with cognition and symptom severity. <i>TCF4 </i>and <i>AKT1</i> are schizophrenia risk genes involved in cognitive functions. The current study examined the interactive effects of <i>TCF4 </i>and <i>AKT1 </i>variants with gender, family history of psychiatric disorders and ethnicity on the AAO of schizophrenia. <b><i>Methods:</i></b> This study consisted of 322 patients with schizophrenia meeting the DSM-IV criteria. Six single nucleotide polymorphisms (SNPs) of <i>TCF4</i> (rs12966547, rs8766, rs2958182, rs9960767, rs10401120 and rs17512836) and seven <i>AKT1</i> SNPs (rs2498804, rs3803304, rs2494732, rs3730358, rs1130214, rs2498784 and rs3803300) were genotyped using the TaqMan® SNP genotyping-based assays method. The relationship of AAO with each variant was investigated using analyses of covariance. <b><i>Results:</i></b> Among the <i>TCF4</i> variants, rs12966547 (p = 0.024) and rs8766 (p = 0.021) were significantly associated with earlier AAO. We found a lower average AAO in patients with the AA genotype of rs12966547, while the CT genotype of rs8766 was demonstrated to have a protective effect on AAO. For rs8766, there was significant gene × gender interaction (p = 0.012) in influencing AAO. However, these results were not significant after false discovery rate correction. Significant gene × ethnicity interactions were observed to influence AAO (p < 0.05). The Kaplan-Meier curve of the minor AA genotype of rs12966547 displayed a significant trend (p = 0.008) for onset after 19 years of age. Similarly, the minor CC genotype of rs8766 showed a significantly (p = 0.034) lower AAO compared to the TT genotype. <b><i>Conclusion:</i></b> Our analyses suggest that individual risk genotypes may influence the risk of schizophrenia in an age-specific manner.



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