The GEN-SCRIP Study (GENetics of SChizophRenia in Pakistan)

GEN-SCRIP 研究（巴基斯坦精神分裂症的遗传学）

• 批准号: 9291116
• 负责人: JAMES A KNOWLES
• 金额: $ 61.24万
• 依托单位: SUNY DOWNSTATE MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-15 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9291116
• 关键词: Adoption; Affect; Award; Biological; Caucasians; Cells; Characteristics; Collection; Communities; Consanguinity; Consent; Copy Number Polymorphism; Costs and Benefits; Custom; DNA; DSM-IV; Data; Deposition; Direct Costs; Disease; Enrollment; Ethnic Origin; European; Facilities and Administrative Costs; Family; Family Sizes; Follow-Up Studies; Funding; Genes; Genetic; Genetic Predisposition to Disease; Genetic Risk; Genetic study; Genome; Genomics; Genotype; Goals; Haplotypes; Human Genetics; Human Inbreeding; Individual; Inherited; Institutes; Intellectual functioning disability; Intervention; Investments; Linkage Disequilibrium; Mental disorders; Modeling; National Institute of Mental Health; Pakistan; Participant; Patients; Phenotype; Population; Population Group; Proteins; Psychiatrist; Publishing; Recording of previous events; Research; Risk; Running; SNP array; Sample Size; Sampling; Schizophrenia; Site; South Asian; Structure; Target Populations; Testing; Transcript; Twin Multiple Birth; Universities; Variant; Vertebral column; base; case control; cohort; cost; cost effective; data sharing; database of Genotypes and Phenotypes; design; effective therapy; family genetics; genetic variant; genome wide association study; genome-wide; neural circuit; phenotypic data; population stratification; psychogenetics; repository; sample collection; screening; trait; treatment strategy; working group

Schizophrenia affects about 1 percent of the world population. We do not currently understand the biological underpinnings of schizophrenia well enough to design effective treatment strategies. Twin and adoption studies supported a genetic etiology. It is becoming clear that its inheritance is partitioned between the rare and common variants in hundreds of genes, each one having a small effect. The sample size required to elucidate the genetic etiology of schizophrenia can be achieved through large scale collaborative efforts, which are currently ongoing. A study published by Psychiatric Genomics Consortium in 2014 identified 108 Genome- Wide significant loci associated for the disorder in samples with European ancestry. Although it was an important milestone in schizophrenia genetics these loci only explain a small proportion of the genetic variance. Expansion of this approach in size, and to other population groups, is required to discovery of additional genetic variants associated with schizophrenia. We propose to ascertain and collect 10,000 cases and 10,000 controls from Pakistan. We have already ascertained and collected 2,000 cases and 1,000 controls. We have formed a consortium of Pakistani psychiatrists at 12 centers. These samples will be genotyped at Stanley Center for Psychiatric Research with Illumina Global Screening Array (GSA), which will contain a backbone of ~660,000 SNPs, which provides LD coverage and imputation accuracy of >0.8, for over 87% of the South Asian genome. There is a strong tradition of consanguineous marriages in Pakistan which has an advantage for genetic studies, especially of recessively inherited traits. We will analyze these data for common SNPs, haplotypes, and copy number variations (CNVs). In association analysis we will examine for recessive inheritance, in addition to additive models of common variants to disease. We will perform a homozygosity mapping to identify regions that are enriched for Runs of Homozygosity (ROH) in cases, as compared to controls. This population will have a different linkage disequilibrium structure which will help to narrow down the genomic intervals containing the potential causative variants at the 108 loci identified in the Caucasian Genome Wide Association Study. We will share these data with broader scientific community via the Psychiatric Genomics Consortium and dbGaP.

精神分裂症影响着世界人口的约 1%。我们目前还不了解生物学 精神分裂症的基础足以设计有效的治疗策略。双胞胎和收养研究 支持遗传病因学。越来越明显的是，它的遗产在稀有和稀有之间划分。 数百个基因中的常见变异，每一种都有很小的影响。阐明所需的样本量 精神分裂症的遗传病因学可以通过大规模的合作努力来实现，这些努力是 目前正在进行中。精神病学基因组学联盟 2014 年发表的一项研究确定了 108 个基因组 欧洲血统样本中与该疾病相关的广泛显着位点。虽然那是一个 精神分裂症遗传学的重要里程碑这些基因座仅解释了一小部分遗传 方差。 需要将这种方法的规模扩大到其他人群，以发现更多 与精神分裂症相关的遗传变异。我们建议查明并收集10,000个案例和10,000个 来自巴基斯坦的控制。我们已经查明并收集了 2,000 个病例和 1,000 个对照。我们有 成立了一个由 12 个中心的巴基斯坦精神病学家组成的联盟。这些样本将在斯坦利进行基因分型 拥有 Illumina Global Screening Array (GSA) 的精神病学研究中心，该中心将包含 约 660,000 个 SNP，为超过 87% 的南方地区提供 LD 覆盖率和 >0.8 的插补精度 亚洲基因组。巴基斯坦有着浓厚的近亲结婚传统，具有优势 用于遗传学研究，特别是隐性遗传性状的研究。我们将分析这些数据中常见的 SNP， 单倍型和拷贝数变异 (CNV)。在关联分析中，我们将检查隐性 遗传，以及常见疾病变异的附加模型。我们将进行纯合性检查 映射以识别病例中纯合性运行 (ROH) 富集的区域，与 控制。该群体将具有不同的连锁不平衡结构，这将有助于缩小范围 基因组间隔包含在白种人中鉴定的 108 个基因座的潜在致病变异 全基因组关联研究。我们将通过以下方式与更广泛的科学界分享这些数据 精神病基因组学联盟和 dbGaP。