A genome-wide association study of schizophrenia in Ireland

描述（由申请人提供：全基因组关联（GWA）被广泛认为是研究复杂疾病（如精神分裂症）的常见疾病/常见变异（CDCV）假说的最强大、最系统和最无偏见的遗传方法。我们建议对以前在爱尔兰收集的种族同质样本进行精神分裂症的单阶段GWA研究。2357个受影响的个体和2000或5000个对照的样本提供了相当大的力量来检测适度影响的基因。我们的总体目标是有助于确定影响精神分裂症易感性的遗传变异。为了实现这一点，我们计划1）收集样本中每个成员的900，000个个体DNA多态性基因型，2）对该数据进行与精神分裂症相关性的初步分析，并在二次分析中3）基于先前的遗传或生物学数据、其他可用的表型数据和疾病的临床特征评估加权显著性检验，以及4）评估多位点，途径和系统关联，以及5）重新联系，重新同意和重新采样受影响的个人贡献NIMH库。公共卫生相关性：精神分裂症是一种常见的，通常是严重的精神疾病，人口频率约为1%;在美国或其他人群中，有相当数量的人受到影响。这种疾病是一个主要的公共卫生负担，因为它发病早，非致命的过程，许多病人需要长期护理。

DESCRIPTION (provided by applicant: Genome-wide association (GWA) is widely viewed as the most powerful, systematic and unbiased genetic approach to the study of the common disease/common variant (CDCV) hypothesis of complex disorders like schizophrenia. We propose to conduct a single- stage GWA study of schizophrenia in an ethnically homogeneous sample previously collected in Ireland. The sample of 2357 affected individuals and 2000 or 5000 controls provides considerable power to detect genes of modest effect. Our overall goal is to contribute to the conclusive identification of genetic variation that influences the liability to schizophrenia. In order to achieve this, we plan to 1) collect 900,000 individual DNA polymorphism genotypes for each member of the sample, 2) perform a primary analysis of this data for association with schizophrenia, and in secondary analyses to 3) assess weighted significance testing based on prior genetic or biological data, other phenotype data available and clinical features of illness, and 4) assess multi-locus, pathway and system associations, and 5) to recontact, reconsent and resample the affected individuals for contribution to the NIMH repository. PUBLIC HEALTH RELEVANCE: Schizophrenia is a common and often severe mental illness with a population frequency of ~1 percent; substantial numbers of individuals in the US or other populations are affected. The illness is a major public health burden because of the early onset, non-fatal course and need for long-term care for many patients.