Identifying the genetic causes of depression in a deeply phenotyped population from South Korea

项目摘要 这个项目解决了需要更好地了解抑郁症的原因（MDD） 作为改善世界上主要残疾原因的诊断和治疗的一种方式。遗传方法，a 确定因果因素，从而找到新的治疗方法的途径，在一些精神病患者中证明是成功的。 疾病，但它们在MDD中的应用带来了挑战，由于条件的异质性和 环境因素的重要性。成功的研究需要通过评估来考虑异质性 多种临床特征，并包括环境风险因素的测量。此外，遗传学研究需要 扩大其覆盖范围，以包括多个不同种族的人口，从而确定更多的风险地点， 使精细映射和可能的因果变异的识别，并扩大多基因预测的使用 更多的人感染疾病。NIMH，在发布PAR-20-026，“精神疾病的遗传结构， 我们认识到这一需要，并响应这一呼吁， 来自韩国和美国的调查人员的国际合作， 在东亚进行大规模的精神病遗传学研究。我们将创建最大的东亚队列， 发现新的MDD基因，增加基因发现工作的多样性（朝着减少 健康差异），并进行详尽的分析，以确定可能的因果变异和基因参与MDD。 目的1：从韩国收集DNA样本和表型 从10,000名患有重度复发性抑郁症的妇女和10,000名匹配的筛查对照中。我们将获得 一套全面的临床特征和风险因素，一套深层次的表型，提供了强大的资源 用于基因鉴定。目的2：我们将对样本进行基因分型，在韩国样本中绘制MDD的风险位点， 异质性的来源，并研究基因和环境如何相互作用，导致MDD。目标3：确定 在东亚队列的荟萃分析中，对MDD特异性遗传位点进行分析，并细化可能的因果变异集 通过在不同种族的队列中使用跨祖先精细映射。

PROJECT SUMMARY This project addresses the need for a better understanding of the causes of major depressive disorder (MDD) as a way to improve diagnosis and treatment for the world's leading cause of disability. Genetic approaches, a path to identifying causal factors and hence finding novel treatments, are proving successful in some psychiatric disorders, but their application in MDD poses challenges, due to the condition's heterogeneity and the importance of environmental factors. Success requires studies that take into account heterogeneity by assessing multiple clinical features, and include measures of environmental risk factors. Furthermore, genetic studies need to expand their reach to include multiple, ethnically diverse populations, so as to identify additional risk loci, enable fine-mapping and the identification of likely causal variants, and expand the use of polygenic predictors of disease to more populations. NIMH, in issuing PAR-20-026, “Genetic Architecture of Mental Disorders in Ancestrally Diverse Populations”, recognizes this need and in response to this call, we have established an international collaboration of investigators from South Korea and the United States, with a strong track record of large-scale psychiatric genetic research in East Asia. We will create the largest East Asian cohort available for the discovery of new MDD genes, increase the diversity of genetic discovery efforts (a step towards reducing health disparities), and perform exhaustive analyses to identify likely causal variants and genes involved in MDD. The aims of the consortium are as follows: Aim 1: To collect from South Korea DNA samples and phenotypes from 10,000 women with severe recurrent MDD and from 10,000 matched, screened, controls. We will obtain a comprehensive set of clinical features and risk factors, a deep set of phenotypes that provide a powerful resource for gene identification. Aim 2: We will genotype samples, map risk loci for MDD in the Korean sample, identify sources of heterogeneity and examine how genes and environment interact to cause MDD. Aim 3: Identify genetic loci specific for MDD in a meta-analysis of East Asian cohorts, and refine likely sets of causal variants by using trans-ancestry fine-mapping in cohorts of different ethnicities.