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

确定韩国深层表型人群抑郁症的遗传原因

基本信息

批准号：
10470895
负责人：
Yong Min Ahn
金额：
$ 162.84万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-17 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10470895
关键词：
Address Adult African American Age Alcohol abuse Anxiety Disorders Bayesian Method Biological Bipolar Disorder Calendar Characteristics Child Abuse China Chinese Clinical Collaborations Collection DNA Data Data Set Detection Diagnosis Disease Drug abuse East Asian Ensure Environment Environmental Exposure Environmental Risk Factor Ethnic Origin European Exclusion Criteria Failure Far East Genes Genetic Genetic Research Genetic Variation Genetic study Genotype Haplotypes Heterogeneity Hispanic Hospitals Individual International Interview Interviewer Joints Korea Koreans Linear Models Linkage Disequilibrium Location Major Depressive Disorder Maps Measures Mental Depression Mental Retardation Mental disorders Meta-Analysis Moods National Institute of Mental Health Outcome Pathogenesis Pathway interactions Patient Self-Report Pattern Phenotype Population Population Heterogeneity Predisposition Recording of previous events Recurrence Reduce health disparities Reporting Research Personnel Resources Risk Factors Sampling Schedule Signal Transduction Social support Source South Korea Stressful Event Structure Subgroup Tablets Training United States Variant Veterans Woman base biobank causal variant cognitive change cohort comorbidity depressive symptoms disability disease heterogeneity ethnic diversity exhaustion experience gene discovery genetic approach genetic architecture genetic risk factor genome wide association study genomic locus grandparent improved inclusion criteria life history multi-ethnic negative affect non-affective psychoses novel precision medicine programs psychiatric genomics psychogenetics rare variant recruit response risk variant sample collection sex success whole genome

项目摘要

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.

项目概要该项目旨在满足更好地了解重度抑郁症 (MDD) 病因的需求作为改善世界上导致残疾的主要原因的诊断和治疗的一种方法。识别因果因素并因此寻找新的治疗方法的方法在某些精神科疾病中被证明是成功的疾病，但由于病情的异质性和MDD的应用带来了挑战环境因素的重要性需要通过评估来考虑异质性的研究。多种临床特征，包括环境风险因素的测量，此外，还需要进行遗传学研究。扩大其覆盖范围以涵盖多个种族不同的人群，以确定其他风险位点，实现精细绘图和识别可能的因果变异，并扩大多基因预测因子的使用 NIMH 发布 PAR-20-026，“精神疾病的遗传结构”。 “祖先多样化的人口”，认识到这一需求，并响应这一号召，我们建立了一个韩国和美国调查人员的国际合作，具有良好的记录我们将在东亚建立最大的东亚队列研究。新 MDD 基因的发现，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，以确定可能与 MDD 相关的因果变异和基因。该联盟的目标如下：目标 1：从韩国收集 DNA 样本和表型我们将从 10,000 名患有严重复发性 MDD 的女性和 10,000 名经过匹配、筛选的对照中获得一份。一套全面的临床特征和风险因素，一套深层的表型，提供了强大的资源目标 2：我们将对样本进行基因分型，绘制韩国样本中 MDD 的风险位点，并进行识别。异质性来源并检查基因和环境如何相互作用导致 MDD。在东亚人群的荟萃分析中找出 MDD 特有的基因位点，并细化可能的因果变异组通过在不同种族的群体中使用跨祖先精细绘图。