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

精神分裂症影响了世界人口的1%。我们目前还不了解 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清楚的是，它的继承是在稀有和 数百个基因中的常见变异，每一个都有很小的影响。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， 目前正在进行中。2014年，精神病基因组学联盟发表的一项研究确定了108个基因组， 在具有欧洲血统的样本中，广泛的显著基因座与该疾病相关。虽然是 精神分裂症遗传学中的重要里程碑这些基因座只能解释一小部分遗传 方差 需要扩大这种方法的规模，并扩大到其他人群，以发现更多的 与精神分裂症相关的遗传变异我们建议查明和收集10，000起案件， 控制巴基斯坦。我们已经确定和收集了2,000例病例和1,000例对照。我们有 在12个中心成立了一个巴基斯坦精神病学家联盟。这些样本将在斯坦利进行基因分型 精神病学研究中心与Illumina全球筛查阵列（GSA），其中将包含一个骨干， ~ 660，000个SNP，为超过87%的南方提供LD覆盖率和>0.8的插补准确度 亚洲基因组。在巴基斯坦有着浓厚的近亲结婚传统， 用于遗传学研究，特别是遗传性状的研究。我们将分析这些数据中常见的SNP， 单倍型和拷贝数变异（CNVs）。在关联分析中，我们将检查隐性 遗传，以及常见疾病变异的加性模型。我们将进行纯合性分析 作图以鉴定在病例中富集纯合性缺失（ROH）的区域，与 对照这个群体将有一个不同的连锁不平衡结构，这将有助于缩小 在高加索人中鉴定的108个基因座上含有潜在致病变异的基因组间隔 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。

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.