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）

基本信息

批准号：
10161831
负责人：
JAMES A KNOWLES
金额：
$ 0.43万
依托单位：
SUNY DOWNSTATE MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-15 至 2022-03-16
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10161831
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 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 causal variant cohort cost cost effective data sharing database of Genotypes and Phenotypes design effective therapy family genetics genetic variant genome wide association study genome-wide genomic locus neural circuit phenotypic data population stratification psychiatric genomics psychogenetics repository sample collection schizophrenia risk screening trait treatment strategy working group

项目摘要

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.

精神分裂症影响着大约1％的世界人口。我们目前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。很明显，其继承已被划分在稀有和数百个基因中的常见变体，每个基因的作用较小。阐明所需的样本量精神分裂症的遗传病因可以通过大规模的协作努力来实现目前正在进行。精神基因组学联盟发表的一项研究于2014年确定了108个基因组 - 与欧洲血统样本中该疾病相关的广泛的基因座。虽然这是一个精神分裂症遗传学中的重要里程碑这些基因座仅解释了一小部分遗传方差。发现这种方法的扩展和其他人口群体需要发现其他与精神分裂症相关的遗传变异。我们建议确定并收集10,000例和10,000例来自巴基斯坦的控制。我们已经确定并收集了2,000例和1,000例对照。我们有在12个中心组成了一个巴基斯坦精神科医生联盟。这些样品将在斯坦利进行基因分型 Illumina全球筛查阵列（GSA）的精神病研究中心，其中将包含一个骨干〜660,000个SNP，可提供LD覆盖范围和归合精度> 0.8，超过87％的南方亚洲基因组。巴基斯坦有一个牢固的近亲婚姻传统，这有一个优势用于遗传研究，尤其是隐性遗传性状。我们将分析这些数据的常见SNP，单倍型和复制号变化（CNV）。在关联分析中，我们将检查隐性继承，除了疾病的常见变体的加性模型外。我们将执行纯合性绘制以识别在情况下富含纯合性（ROH）的区域，相比之下控件。该人群将具有不同的连锁不平衡结构，这将有助于缩小在高加索人中鉴定出的108个基因座的潜在因果变异的基因组间隔基因组广泛的关联研究。我们将通过精神病基因组学联盟和DBGAP。