| 1 | Mol. Psychiatry 2009 Jan 14: 30-6 |
|---|---|
| PMID | 18813210 |
| Title | Analysis of 10 independent samples provides evidence for association between schizophrenia and a SNP flanking fibroblast growth factor receptor 2. |
| Abstract | 我们和其他人以前已经报告了与schizophrenia在10q25-Q26染色体上，但迄今为止，该地区的敏感性基因尚未鉴定。我们检查了来自3606个单核苷酸多态性（SNP）映射到10q25-Q26的数据，该数据已在全基因组关联研究（GWAS）中键入10q25-Q26。schizophrenia(479 UK cases/2937 controls). SNPs with P<0.01 (n=40) were genotyped in an additional 163 UK cases and those markers that remained nominally significant at P<0.01 (n=22) were genotyped in replication samples from Ireland, Germany and Bulgaria consisting of a total of 1664 cases withschizophreniaand 3541 controls. Only one SNP, rs17101921, was nominally significant after meta-analyses across the replication samples and this was genotyped in an additional six samples from the United States/Australia, Germany, China, Japan, Israel and Sweden (n=5142 cases/6561 controls). Across all replication samples, the allele at rs17101921 that was associated in the GWAS showed evidence for association independent of the original data (OR 1.17 (95% CI 1.06-1.29), P=0.0009). The SNP maps 85 kb from the nearest gene encoding fibroblast growth factor receptor 2 (FGFR2) making this a potential susceptibility gene forschizophrenia. |
| SCZ关键字 | schizophrenia |
| 2 | Am. J. Hum. Genet. 2012 Feb 90: 175-200 |
| PMID | 22325359 |
| Title | Paternal age effect mutations and selfish spermatogonial selection: causes and consequences for human disease. |
| Abstract | Advanced paternal age has been associated with an increased risk for spontaneous congenital disorders and common complex diseases (such as some cancers,schizophrenia, and autism), but the mechanisms that mediate this effect have been poorly understood. A small group of disorders, including Apert syndrome (caused byFGFR2突变），adnondroploploploploploploploploplasia（FGFR3）和Costello综合征（HRAS），我们共同称其为“父亲年龄效应”（PAE）疾病，为研究这种现象的生物学和分子基础提供了一个良好的模型。来自精子和睾丸中PAE突变的直接定量的最新证据表明，父亲年龄效应的共同因素在于精子细胞行为的失调，这种效应通过生长因子受体受体-RAS信号转导途径介导的分子介导。数据表明，PAE突变虽然很少出现，但在正常睾丸中通过类似于肿瘤发生的过程进行了正常睾丸的积极选择。这种克隆膨胀可能发生在所有男性的睾丸中，导致突变精子的相对富集在时间上散布，以解释与这些疾病相关的观察到的父亲年龄效应，并且在极少数情况下与睾丸肿瘤形成。由于对RAS和其他细胞增殖和存活的调节在许多不同的生物学环境中很重要，例如在肿瘤发生，器官稳态和神经发生期间包括复杂疾病的疾病，例如神经认知疾病和癌症易感性。 |
| SCZ关键字 | schizophrenia |
| 3 | World J. Biol. Psychiatry 2012 Dec 13: 599-604 |
| PMID | 22404656 |
| Title | FGFR2is associated with bipolar disorder: a large-scale case-control study of three psychiatric disorders in the Chinese Han population. |
| Abstract | Repetitive linkage analyses have indicated 10q25-q26 as a shared risk region forschizophrenia(SCZ) and bipolar disorder (BPD). A genome-wide association study and follow-up recently identified a significant association between a single nucleotide polymorphism (SNP) of this region (rs17101921) and SCZ. The nearest gene to this SNP is fibroblast growth factor receptor 2 (FGFR2). We carried out a large scale case-control study to test the association betweenFGFR2and three major psychiatric disorders: SCZ, BPD and major depressive disorder (MDD) in the Chinese Han population. Eight tag SNPs were genotyped using Taqman assay in 1139 BPD patients, 1112 SCZ patients, 1119 MDD patients and 1135 shared healthy controls. 纠正后的多个tests by permutation, one SNP (rs11199993), and a haplotype including this SNP, was found to be significantly associated with BPD. Potential population stratification in our samples was analyzed using 70 additional random SNPs dispersed on different chromosomes. No population stratification was detected, so our results could not be affected by this cofounding factor. Limitations of our study include incomplete coverage and insufficient power to detect association for relatively small odds ratio. Association betweenFGFR2and BPD is worthy of further confirmation. |
| SCZ关键字 | schizophrenia |
| 4 | Neuroscientist 2013 Oct 19: 479-94 |
| PMID | 23343917 |
| Title | Fibroblast growth factors in neurodevelopment and psychopathology. |
| Abstract | In psychiatric disorders, the effect of genetic and environmental factors may converge on molecular pathways and brain circuits related to growth factor functioning. In this review, we describe how disturbances in fibroblast growth factors (FGFs) and their receptors influence behavior by affecting brain development. Recently, several studies reported associations of members of the FGF family with psychiatric disorders. FGFs are key candidates to modulate the impact of environmental factors, such as stress. Mutant mice for FGF receptor 1 showschizophrenia-like behaviors that are related to general loss of neurons and postnatal glia dysfunction. Mice lacking FGF2, a FGFR1 ligand, show similar reductions in brain volume and hyperactivity, as well as increased anxiety behaviors.FGFR2and FGF17 are involved in the development of frontal brain regions and impairments in cognitive and social behaviors, respectively. Moreover, treatment with FGF2 was beneficial for depressive and cognitive measures in several animal studies and one human study. These findings indicate the importance of the FGF system with respect to developing novel etiology-directed treatments for psychopathology. |
| SCZ关键字 | schizophrenia |