Common variants on 8p12 and 1q24.2 confer risk of schizophrenia
ABSTRACT Schizophrenia is a severe mental disorder affecting ∼1% of the world population, with heritability of up to 80%. To identify new common genetic risk factors, we performed a genome-wide association study (GWAS) in the Han Chinese population. The discovery sample set consisted of 3,750 individuals with schizophrenia and 6,468 healthy controls (1,578 cases and 1,592 controls from northern Han Chinese, 1,238 cases and 2,856 controls from central Han Chinese, and 934 cases and 2,020 controls from the southern Han Chinese). We further analyzed the strongest association signals in an additional independent cohort of 4,383 cases and 4,539 controls from the Han Chinese population. Meta-analysis identified common SNPs that associated with schizophrenia with genome-wide significance on 8p12 (rs16887244, P = 1.27 × 10(-10)) and 1q24.2 (rs10489202, P = 9.50 × 10(-9)). Our findings provide new insights into the pathogenesis of schizophrenia.
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- "There are numerous indications that FGFs play a role in schizophrenia and mood disorders (Terwisscha van Scheltinga and others 2009; Turner and others 2006; Turner and others 2012). At the DNA level, single nucleotide polymorphisms (SNPs) near FGFR1 were strongly associated with schizophrenia in a genomewide association study (Shi and others 2011). Second, an SNP located 85 kb from the nearest gene, FGFR2, was the only significant finding after several rounds of replication in a linkage fine mapping study on schizophrenia (O'Donovan and others 2009). "
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 show schizophrenia-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. FGFR2 and 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.The Neuroscientist 01/2013; 19(5). DOI:10.1177/1073858412472399 · 7.62 Impact Factor
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- "However, even for these promising genes, there has been a remarkable failure to replicate exactly the same markers and haplotypes across studies and a lack of consistency in implicating particular alleles in the development of psychosis (Alkelai et al. 2008; Sanders et al. 2008; Sullivan, 2008). Moreover, none of the genome-wide association study (GWAS) on schizophrenia or bipolar disorder so far implicated any of the previously involved candidate genes (Shi et al. 2011; Bergen & Petryshen, 2012). These inconclusive results seem to suggest that phenotype characterization might be particularly important when identifying true and valid candidate genes and that several genes might interact to determine a particular phenotype. "
ABSTRACT: This paper aims at providing an overview of the background, design and initial findings of Psychosis Incident Cohort Outcome Study (PICOS). PICOS is a large multi-site population-based study on first-episode psychosis (FEP) patients attending public mental health services in the Veneto region (Italy) over a 3-year period. PICOS has a naturalistic longitudinal design and it includes three different modules addressing, respectively, clinical and social variables, genetics and brain imaging. Its primary aims are to characterize FEP patients in terms of clinical, psychological and social presentation, and to investigate the relative weight of clinical, environmental and biological factors (i.e. genetics and brain structure/functioning) in predicting the outcome of FEP. An in-depth description of the research methodology is given first. Details on recruitment phase and baseline and follow-up evaluations are then provided. Initial findings relating to patients' baseline assessments are also presented. Future planned analyses are outlined. Both strengths and limitations of PICOS are discussed in the light of issues not addressed in the current literature on FEP. This study aims at making a substantial contribution to research on FEP patients. It is hoped that the research strategies adopted in PICOS will enhance the convergence of methodologies in ongoing and future studies on FEP.Epidemiology and Psychiatric Sciences 06/2012; 21(3):281-303. DOI:10.1017/S2045796012000315 · 3.36 Impact Factor
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ABSTRACT: Background: We performed a genome-wide association study (GWAS) to identify common risk variants for schizophrenia. Methods: The discovery scan included 1606 patients and 1794 controls from Ireland, using 6,212,339 directly genotyped or imputed single nucleotide polymorphisms (SNPs). A subset of this sample (270 cases and 860 controls) was subsequently included in the Psychiatric GWAS Consortium-schizophrenia GWAS meta-analysis. Results: One hundred eight SNPs were taken forward for replication in an independent sample of 13,195 cases and 31,021 control subjects. The most significant associations in discovery, corrected for genomic inflation, were (rs204999, p combined = 1.34 x 10(-9) and in combined samples (rs2523722 p combined = 2.88 x 10(-16)) mapped to the major histocompatibility complex (MHC) region. We imputed classical human leukocyte antigen (HLA) alleles at the locus; the most significant finding was with HLA-C*01:02. This association was distinct from the top SNP signal. The HLA alleles DRB1*03:01 and B*08:01 were protective, replicating a previous study. Conclusions: This study provides further support for involvement of MHC class I molecules in schizophrenia. We found evidence of association with previously reported risk alleles at the TCF4, VRK2, and ZNF804A loci.Biological Psychiatry 10/2012; 72(8-8):620-628. DOI:10.1016/j.biopsych.2012.05.035 · 10.25 Impact Factor