A genomewide linkage study of age at onset in schizophrenia
ABSTRACT There is strong evidence for a genetic contribution to age at onset of schizophrenia, which probably involves both susceptibility loci for schizophrenia and modifying loci acting independent of disease risk. We sought evidence of linkage to loci that influence age at onset of schizophrenia in a sample of 94 affected sibling pairs with DSM-IV schizophrenia or schizoaffective disorder, and age at first psychiatric contact of 45 years or less. Individuals were genotyped for 229 microsatellite markers spaced at approximately 20 cM intervals throughout the genome. Loci contributing to age at onset were sought by a quantitative maximum-likelihood multipoint linkage analysis using MAPMAKER/SIBS. A nonparametric multipoint analysis was also performed. The genomewide significance of linkage results was assessed by simulation studies. There were six maximum-likelihood LOD score peaks of 1.5 or greater, the highest being on chromosome 17q (LOD = 2.54; genomewide P = 0.27). This fulfils Lander and Kruglyak's [1995: Nat Genet 11:241-247] criteria for suggestive linkage in that it would be expected to occur once or less (0.3 times) per genome scan. However, this finding should be treated with caution because the LOD score appeared to be almost solely accounted for by the pattern of ibd sharing at one marker (D17S787), with virtually no evidence of linkage over flanking markers. None of the linkage results achieved genomewide statistical significance, but the LOD score peak on chromosome 13q (LOD = 1.68) coincided with the region showing maximum evidence for linkage in the study by Blouin et al. [1998: Nat Genet 20:70-73] of categorical schizophrenia.
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ABSTRACT: Background Estrogen is believed to play an important role in the central nervous system (CNS) and exert a protective role against schizophrenia. Estrogen receptor alpha (ESRα) mediates the biological action of estrogen. Rs2234693 and rs9340799, single nucleotide polymorphisms of ESRα, may be related to many psychiatric disorders, while their association with schizophrenia has not been clarified. Methods Genotypes rs2234693 and rs9340799 were detected in 303 schizophrenic patients and 292 healthy controls in a Chinese population. The positive and negative syndrome scale (PANSS) was used to estimate symptoms and therapeutic effects. The association of these polymorphisms with schizophrenia and clinical characteristics was analyzed by the chi-square test, analysis of variance, and others. Results The distribution of genotypes and allele frequencies of rs2234693 and rs9340799 exhibited no significant differences between patients and controls, while haplotypes consisting of these polymorphisms had significant differences. For 2234693, T-allele carriers had an earlier age at onset. CC-homozygote carriers had a higher general psychopathology score and its percentage reduction in male and paranoid patients, respectively. CC-homozygote carriers had a higher tension (G4) and poor impulse control (G14) score, mainly in paranoid patients. Furthermore, patients with the CC homozygote had higher reductions of G4 and G14 scores when treated by aripirazole and risperidone, respectively. Conclusions Haplotypes consisting of these two polymorphisms in ESRα may be strongly associated with schizophrenia. The rs2234693 was related to age at onset, general psychopathology, G4 and G14 symptoms, even the therapeutic effect in different groups.Behavioral and Brain Functions 03/2013; 9(1):12. DOI:10.1186/1744-9081-9-12 · 2.00 Impact Factor
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ABSTRACT: Schizophrenia is a common psychiatric disorder with high heritability. The age of onset is an important phenotype of schizophrenia and may be under considerable genetic control. Our previous study showed that a single nucleotide polymorphism (SNP) rs139887 in sex-determining region Y-box 10 (SOX10) gene was associated with the age of onset in schizophrenia. The aim of this study was to evaluate the effect of another SNP rs139883 in the exon 4 of SOX10 on schizophrenia using an early-onset samples in the Han Chinese population. A total of 309 schizophrenic patients with onset before age 18 and 390 healthy controls were recruited for association study. No significant differences of allele or genotype frequencies were identified between the schizophrenic patients and controls. However, the C allele was significantly associated with an earlier age of onset in total patients and male patients (Kaplan-Meier log rank test P = 0.026; Kaplan-Meier log rank test P = 0.047, respectively), but not in females. In conclusion, the SOX10 rs139883 polymorphism influenced the age of onset of schizophrenia in a gender-specific manner and this may represent a vital genetic clue for the etiology of schizophrenia.Journal of Molecular Neuroscience 03/2013; 50(2). DOI:10.1007/s12031-013-9982-y · 2.76 Impact Factor
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ABSTRACT: Objectives: MicroRNA137 (miRNA137) regulates several gene expressions involved in brain development, and a recent large genome wide association study (GWAS) revealed a possible association between miRNA137 and schizophrenia. Methods: The allelic variants of rs66642155, a variable number tandem repeat polymorphism, and the single nucleotide polymorphism rs1625579 A/C in the miRNA137 host gene fragment were compared between 300 schizophrenic patients and 300 healthy controls from the Han Chinese population. The association of these polymorphisms with clinical characteristics of schizophrenia was also tested. Results: Genotype and allele frequencies of these polymorphisms were not significantly different between patient and control populations. In patients, however, age at onset was much later in wild type rs66642155 carriers than in mutation carriers. Total positive score on the Positive and Negative Symptom Scale (PANSS), total five-factor model positive score, and the delusions symptom score were all significantly higher in wild type rs66642155 carriers with schizophrenia, while the disturbance of volition symptom score was significantly higher in the mutation carriers with schizophrenia. Conclusions:MiRNA137 may not be a significant susceptibility gene for schizophrenia, but in patients, rs66642155 allelic variant of miRNA137 appears to influence age at onset and the severity of positive symptoms.The International Journal of Psychiatry in Medicine 01/2014; 47(2):153-168. DOI:10.2190/PM.47.2.f · 0.81 Impact Factor