Positive association of schizophrenia to JARID2 gene.
Dysbindin (DTNBP1) is a positional candidate gene for 6p22.3-linked schizophrenia (SZ). However, so far, no disease-causing alleles have been identified. DTNBP1 is immediately adjacent to JARID2, a member of the ARID (AT-rich interaction domain) family of transcription modulators. We have previously suggested that proteins which bind to AT-rich domains could play a role in SZ pathogenesis. Consequently, we explored the possibility that JARID2 itself could be a candidate gene for 6p22.3-linked SZ. We used a case control design to analyze single nucleotide polymorphisms (SNPs) and insertion/deletion variants affecting AT-rich domains in both the DTNBP1 and JARID2 genes. Three of the DTNBP1 SNPs analyzed had previously been shown to be associated with SZ. We did not detect any significant difference in allele, genotype or haplotype distribution for any of these DTNBP1 markers. However, we did detect a significant difference in allele distribution for a tetranucleotide repeat polymorphism in the JARID2 gene that affects an AT-rich domain. A significant increase in short alleles (less than 11 repeats) was found in patients with SZ (chi(2) = 7.02; P = 0.008). No other JARID2 marker displayed statistically significant allele and genotype distributions. Our findings suggest that JARID2 should be viewed as a candidate gene for 6p22.3-linked SZ.
Pedrosa
Erika
E
Department of Psychiatry, Division of Basic Research, Albert Einstein College of Medicine, Bronx, New York, USA.
Ye
Kenny
K
Nolan
Karen A
KA
Morrell
Lauren
L
Okun
Jeffrey M
JM
Persky
Adam D
AD
Saito
Takuya
T
Lachman
Herbert M
HM
D001741:Black or African American / Q000235:genetics; D000483:Alleles; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics; D016022:Case-Control Studies; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases; D018895:Microsatellite Repeats; D010089:Oxidoreductases, N-Demethylating; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*; D044465:White People / Q000235:genetics
D002352:Carrier Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; C432416:DTNBP1 protein, human; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D005819:Genetic Markers; D014157:Transcription Factors; D056484:Jumonji Domain-Containing Histone Demethylases; C494424:KDM4A protein, human; D010089:Oxidoreductases, N-Demethylating