A genome-wide association study of schizophrenia in Ireland

描述(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/共同变异(CDCV)假说的最有效、最系统和最公正的遗传学方法。我们建议对精神分裂症进行一项单一阶段的GWA研究，研究对象是先前在爱尔兰收集的种族同质样本。2357名受影响的个体和2000或5000名对照的样本提供了相当大的能力来检测影响不大的基因。我们的总体目标是对影响精神分裂症易感性的基因变异做出决定性的识别。为了实现这一目标，我们计划1)为样本中的每个成员收集900,000个个体DNA多态基因类型，2)对这些数据进行与精神分裂症有关的初步分析，并在二次分析中3)基于先前的遗传或生物数据、其他可用表型数据和疾病的临床特征评估加权显著性检验，4)评估多基因、途径和系统关联，5)重新联系、重新同意和重新采样受影响的个人，以便为NIMH储存库做出贡献。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%；在美国或其他人口中，有相当数量的人受到影响。该病起病早，病程非致命性，许多患者需要长期护理，是一种主要的公共卫生负担。

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.