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.
Department of Biostatistics and Epidemiology, College of Public Health, East Tennessee State University, Johnson City, TN 37614-1700, USA. wangk@etsu.edu
Ke-Sheng
KS
Wang
Qunyuan
Q
Zhang
Xuefeng
X
Liu
Longyang
L
Wu
Min
M
Zeng
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003072:Cognition Disorders / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D053673:Glypicans / Q000235:genetics; D006239:Haplotypes; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018995:Myosin Heavy Chains / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
C120300:GPC6 protein, human; D053673:Glypicans; D018398:Homeodomain Proteins; C510866:MYH13 protein, human; C117905:PHF2 protein, human; C435984:PKNOX2 protein, human; D014157:Transcription Factors; D018995:Myosin Heavy Chains