PKNOX2 is associated with formal thought disorder in schizophrenia: a meta-analysis of two genome-wide association studies.

Formal thought disorder (FTD), or disorganized speech, is one of the central signs of schizophrenia; however, little is known about the etiology of FTD. To identify new genetic loci associated with FTD, we conducted the first genome-wide association meta-analysis of two datasets of 835 cases of FTD and 2,694 controls with 729,454 single-nucleotide polymorphisms (SNPs). Logistic regression analysis of FTD as a binary trait, adjusted for age and sex, was performed using PLINK. For meta-analysis of two datasets, the fixed-effect model in PLINK was applied. Through meta-analysis we identified 61 SNPs associated with FTD with p < 10(-4). The most significant association with FTD was observed with rs1783925 (p = 4.4 × 10(-7)) within PKNOX2 gene at 11q24.2 while the second interesting locus was rs2277644 (p = 1.18 × 10(-5)) within MYH13 at 17p13. Haplotype analyses of PKNOX2 and MYH13 loci further supported the associations with FTD. The third locus was PHF2 at 9q22.31 (the top SNP was rs12238738 with p = 2.08 × 10(-5)) while the fourth locus was GPC6 at 13q32 (the top SNP was rs17196161 with p = 3.12 × 10(-5)). In conclusion, we identified four new loci (PKNOX2, MYH13, PHF2, and GPC6) associated with FTD. These findings offer the potential for new insights into the pathogenesis of FTD and schizophrenia.

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