A genome-wide association study of schizophrenia in Ireland

描述（由申请人提供）：全基因组关联（GWA）被广泛认为是研究精神分裂症等复杂疾病的常见疾病/常见变异（CDCV）假说的最强大、系统和公正的遗传方法。我们建议在先前在爱尔兰收集的种族同质样本中进行精神分裂症的单阶段GWA研究。2357个受影响个体的样本和2000或5000个对照提供了相当大的能力来检测适度影响的基因。我们的总体目标是为确定影响精神分裂症易感性的遗传变异做出贡献。为了实现这一目标，我们计划1)为每个样本成员收集900,000个个体DNA多态性基因型，2)对这些数据进行与精神分裂症相关的初步分析，并在二次分析中进行3)评估加权显著性测试，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，4)评估多位点，途径和系统关联，5)重新联系。重新同意并重新采样受影响的个人，以贡献给NIMH存储库。公共卫生相关性：精神分裂症是一种常见且通常严重的精神疾病，人口发病率约为1%；在美国或其他人口中有相当数量的人受到影响。该病是一项重大的公共卫生负担，因为许多患者发病早，病程不致命，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.