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Common variants on chromosome 6p22.1 are associated with schizophrenia

机译:6p22.1号染色体上的常见变异与精神分裂症有关

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摘要

Schizophrenia, a devastating psychiatric disorder, has a prevalence of 0.5-1%, with high heritability (80-85%) and complex transmission. Recent studies implicate rare, large, high-penetrance copy number variants in some cases, but the genes or biological mechanisms that underlie susceptibility are not known. Here we show that schizophrenia is significantly associated with single nucleotide polymorphisms (SNPs) in the extended major histo-compatibility complex region on chromosome 6. We carried out a genome-wide association study of common SNPs in the Molecular Genetics of Schizophrenia (MGS) case-control sample, and then a meta-analysis of data from the MGS, International Schizophrenia Consortium and SGENE data sets. No MGS finding achieved genome-wide statistical significance. In the meta-analysis of European-ancestry subjects (8,008 cases, 19,077 controls), significant association with schizophrenia was observed in a region of linkage disequilibrium on chromosome 6p22.1 (P = 9.54 × 10~(-9)). This region includes a histone gene cluster and several immunity-related genes-possibly implicating aetiological mechanisms involving chromatin modification, transcriptional regulation, autoimmunity and/or infection. These results demonstrate that common schizophrenia susceptibility alleles can be detected. The characterization of these signals will suggest important directions for research on susceptibility mechanisms.
机译:精神分裂症是一种毁灭性的精神疾病,患病率为0.5-1%,遗传性较高(80-85%),传播途径复杂。最近的研究暗示了在某些情况下罕见的,大的,高渗透性的拷贝数变异体,但是作为易感性基础的基因或生物学机制尚不清楚。在这里,我们显示精神分裂症与6号染色体扩展的主要组织相容性复杂区域中的单核苷酸多态性(SNP)显着相关。我们在精神分裂症的分子遗传学(MGS)案例中进行了常见SNP的全基因组关联研究-控制样本,然后对来自MGS,国际精神分裂症协会和SGENE数据集的数据进行荟萃分析。没有MGS发现达到全基因组统计意义。在欧洲血统的受试者(8,008例,19,077例对照)的荟萃分析中,在6p22.1染色体上的连锁不平衡区域观察到了与精神分裂症的显着关联(P = 9.54×10〜(-9))。该区域包括一个组蛋白基因簇和几个与免疫相关的基因,可能与病原学机制有关,包括染色质修饰,转录调控,自身免疫和/或感染。这些结果表明可以检测到常见的精神分裂症易感性等位基因。这些信号的表征将为研究敏感性机制提供重要的方向。

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  • 来源
    《Nature》 |2009年第7256期|753-757|共5页
  • 作者单位

    Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California 94304, USA;

    Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California 94304, USA;

    Center for Psychiatric Genetics, NorthShore University HealthSystem Research Institute, Evanston, Illinois 60201, USA;

    Center for Psychiatric Genetics, NorthShore University HealthSystem Research Institute, Evanston, Illinois 60201, USA;

    Center for Psychiatric Genetics, NorthShore University HealthSystem Research Institute, Evanston, Illinois 60201, USA;

    Department of Computer Science, Columbia University, New York, New York 10027, USA;

    Medical Research Council-Biostatistics Unit, Institute of Public Health, Cambridge CB2 2SR, UK;

    MRC Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Heath Park, Cardiff CF23 6BQ, UK;

    Department of Health Research and Policy, Stanford University, Stanford, California 94304, USA;

    Queensland Centre for Mental Health Research, and Queensland Institute for Medical Research, Brisbane, Queensland 4072, Australia;

    Department of Psychiatry, University of Colorado Denver, Aurora, Colorado 80045,USA;

    Department of Psychiatry and Behavioral Sciences, Atlanta Veterans Affairs Medical Center, and Emory University, Atlanta, Georgia 30322, USA;

    Department of Psychiatry,Washington University, St Louis, Missouri 63110, USA;

    Department of Psychiatry, Mount Sinai School of Medicine, New York, New York 10029, USA;

    School of Nursing, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA;

    Department of Psychiatry, University of California at San Francisco, San Francisco, California 94143,USA;

    Mentai Health Clinical Research Center, and Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA;

    Mentai Health Clinical Research Center, and Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA;

    Department of Neurology,School of Medicine, University of California at San Francisco, San Francisco, California 94143, USA;

    Center for Genotyping and Analysis, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA;

    Departments of Psychiatry, and Human Genetics, Virginia Commonwealth University, Richmond, Virginia 23298, USA;

    Department of Psychiatry, University of Colorado Denver, Aurora, Colorado 80045,USA;

    Center for Psychiatric Genetics, NorthShore University HealthSystem Research Institute, Evanston, Illinois 60201, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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