Whole genome sequencing of bipolar disorder and schizophrenia

描述（由申请人提供）：我们计划收集并分析来自精神分裂症（SCZ，n=150）、双相情感障碍（BPD，n=150）和对照组（n=100）患者的首次全基因组序列数据。通过首次对精神疾病个体的遗传变异进行全面评估，我们将为未来SCZ和BPD的遗传研究奠定基础。对于许多常见疾病，大规模全基因组关联研究（GWAS）最近发现了新的遗传风险因素，通常在以前未被怀疑的基因或非编码区。家族和双胞胎研究已经确定遗传因素在SCZ和BPD风险中起主要作用，GWAS研究指出罕见遗传和从头拷贝数变异以及常见SNP的重要作用。我们将使用新一代测序技术获得400个样本的全基因组DNA序列。目标1：从我们具有GWAS数据的> 18，000个样品中，我们将从瑞典样品中选择SCZ和BPD患者，其富集了疾病家族史，我们对其进行了匹配的对照，并且从美国样品中选择富集了散发病例，其亲本DNA样品是可用的。进行全基因组测序以识别DNA变异。目标2：开发一个分析框架，用于注释、管理和查询与疾病状态有关的遗传数据。目标3：后续测序结果，包括计算机基因分型、3000名个体目标区域的深度测序以及超过18，000名个体的特定变异基因分型。所有数据和软件工具都将作为资源提供给更广泛的社区。 公共卫生相关性：叙述：我们将使用下一代高通量技术获得精神分裂症和双相情感障碍患者以及匹配对照的全基因组序列数据，以发现可能与这些疾病相关的新遗传变异。它们是影响数百万美国人的大型公共卫生问题，并且没有有效的治疗方法。

DESCRIPTION (provided by applicant): We propose to collect and analyze the first ever whole genome sequence data from patients with schizophrenia (SCZ, n=150), bipolar disorder (BPD, n=150) and controls (n=100). By providing the first comprehensive evaluation of genetic variation in individuals with psychiatric disease we will lay the foundation for future genetic studies of SCZ and BPD. For many common diseases, large-scale genome-wide association studies (GWAS) have recently identified new genetic risk factors, typically in previously unsuspected genes or non-coding regions. Family and twin studies have conclusively established that heritable factors play the major role in SCZ and BPD risk, and GWAS studies have pointed to important roles for rare inherited and de novo copy number variants as well as common SNPs. We will use next generation sequencing technology to obtain whole genome DNA sequence for 400 samples. Aim 1: From among the >18,000 samples for whom we have GWAS data we will select SCZ and BPD patients from a Swedish sample, enriched for family- history of disease, for whom we have matched controls, and from a US sample enriched for sporadic cases, for whom parental DNA samples are available. Perform whole genome sequencing to identify DNA variation. Aim 2: Develop an analytic framework to annotate, curate and query the genetic data with respect to disease status. Aim 3: Follow-up sequencing results, including in silico genotyping, deep sequencing of targeted regions in 3000 individuals and genotyping specific variants in over 18,000 individuals. All data and software tools will be made available as a resource to the broader community. PUBLIC HEALTH RELEVANCE: Narrative: We will obtain whole genome sequence data using next generation high-throughput technology in patients with schizophrenia and bipolar disorder and matched controls to find new genetic variation that may be associated with these diseases. They are large public health problems affecting millions of Americans and have no effective treatments.