TY - JOUR
T1 - Interleukin 3 and schizophrenia
T2 - The impact of sex and family history
AU - Chen, X.
AU - Wang, X.
AU - Hossain, S.
AU - O'Neill, F. A.
AU - Walsh, D.
AU - Van Den Oord, E.
AU - Fanous, A.
AU - Kendler, K. S.
N1 - Funding Information:
This study is supported by a research grant (RO1MH41953) to KSK from the National Institute of Mental Health and by a young investigator award to XC from the National Alliance for Research on Schizophrenia and Depression. We thank the patients and their families for participating in this study.
PY - 2007/3
Y1 - 2007/3
N2 - Chromosome 5q21-33 has been implicated in harboring risk genes for schizophrenia. In this paper, we report evidence that multiple single nucleotide polymorphisms in and around interleukin 3 (IL3) are associated with the disease in the Irish Study of High-Density Schizophrenia Families (ISHDSF), the Irish Case-Control Study of Schizophrenia (ICCSS) and the Irish Trio Study of Schizophrenia (ITRIO). The associations are sex-specific and depend on the family history (FH) of schizophrenia. In all three samples, rs31400 shows female-specific and FH-dependent associations (P=0.0062, 0.0647 and 0.0284 for the ISHDSF, ICCSS and ITRIO, respectively). Several markers have similar associations in one or two of the three samples. In haplotype analyses, identical risk and protective haplotypes are identified in the ISHDSF and ITRIO samples in several multimarker combinations. For ICCSS, the same haplotypes are implicated; however, the risk haplotypes observed in the family samples become protective. Several significant markers, rs440970, rs31400 and rs2069803, are located in and around known estrogen response elements, promoter and enhancer of the IL3 gene. They may explain the sex-specific associations and be functional for the expression of IL3 gene.
AB - Chromosome 5q21-33 has been implicated in harboring risk genes for schizophrenia. In this paper, we report evidence that multiple single nucleotide polymorphisms in and around interleukin 3 (IL3) are associated with the disease in the Irish Study of High-Density Schizophrenia Families (ISHDSF), the Irish Case-Control Study of Schizophrenia (ICCSS) and the Irish Trio Study of Schizophrenia (ITRIO). The associations are sex-specific and depend on the family history (FH) of schizophrenia. In all three samples, rs31400 shows female-specific and FH-dependent associations (P=0.0062, 0.0647 and 0.0284 for the ISHDSF, ICCSS and ITRIO, respectively). Several markers have similar associations in one or two of the three samples. In haplotype analyses, identical risk and protective haplotypes are identified in the ISHDSF and ITRIO samples in several multimarker combinations. For ICCSS, the same haplotypes are implicated; however, the risk haplotypes observed in the family samples become protective. Several significant markers, rs440970, rs31400 and rs2069803, are located in and around known estrogen response elements, promoter and enhancer of the IL3 gene. They may explain the sex-specific associations and be functional for the expression of IL3 gene.
KW - Association
KW - Family history
KW - Interleukin 3
KW - Linkage disequilibrium test
KW - Schizophrenia
KW - Sex
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U2 - 10.1038/sj.mp.4001932
DO - 10.1038/sj.mp.4001932
M3 - Article
C2 - 17179997
AN - SCOPUS:33847324016
SN - 1359-4184
VL - 12
SP - 273
EP - 282
JO - Molecular Psychiatry
JF - Molecular Psychiatry
IS - 3
ER -