Genetic association and post-mortem brain mRNA analysis of DISC1 and related genes in schizophrenia.
Convergent evidence from genetic linkage, genetic association and biological studies implicates the Disrupted in schizophrenia 1 (DISC1) gene in the etiology and pathophysiology of schizophrenia. We conducted genetic association studies in matched case-control and family sample sets (N=117 families; N=210 case-control pairs), testing polymorphisms across DISC1 and DISC1 interacting genes: LIS1, NUDEL, FEZ1 and PDE4B. We found that DISC1 variants, particularly in the exon 9/intron 9/intron 10 region of the gene, may be associated with risk for schizophrenia in our sample population. There was no strong evidence for association with LIS1, NUDEL, FEZ1 and PDE4B. Gene-gene interaction analyses and mRNA quantification in post-mortem brains from schizophrenia patients and control subjects did not reveal significant differences.
Rastogi
Anjali
A
Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, Canada.
Zai
Clement
C
Likhodi
Olga
O
Kennedy
James L
JL
Wong
Albert H
AH
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000235:genetics; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D001921:Brain / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics; D016022:Case-Control Studies; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000235:genetics; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005787:Gene Frequency; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011180:Postmortem Changes; D012333:RNA, Messenger / Q000378:metabolism*; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C412476:DISC1 protein, human; C528597:FEZ1 protein, human; D008869:Microtubule-Associated Proteins; C421108:NDEL1 protein, human; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C084102:PAFAH1B1 protein, human; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C517360:PDE4B protein, human