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：
10654686
负责人：
Yong Min Ahn
金额：
$ 189.29万
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/10654686
关键词：
Address Adult African American Age Alcohol abuse Anxiety Disorders Bayesian Method Biological Bipolar Disorder Calendar Characteristics Child Abuse China Chinese Chromosome Mapping Clinical Collaborations Collection DNA Data Data Set Detection Diagnosis Disease Drug abuse East Asian 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 causal variant cognitive change cohort comorbidity depressive symptoms disability disease heterogeneity ethnic diversity 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 phenotypic data 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.

项目摘要该项目解决了对重大抑郁症（MDD）的理解的必要性作为改善世界残疾主要原因的诊断和治疗方法的一种方式。遗传方法，a 识别因果因素并因此找到新的治疗方法，在某些精神科中证明是成功的疾病，但由于疾病的异质性和环境因素的重要性。成功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度量。此外，遗传研究需要将其覆盖范围扩大到包括多个种族多样的人群，以确定额外的风险基因座，启用精细映射和可能因果变体的识别，并扩展使用多基因预测变量疾病对更多人群。 NIMH，在发布Par-20-026时，“精神障碍的遗传结构祖先多样化的人群”，认识到这一需求，并在回应这个电话中，我们已经建立了一个来自韩国和美国调查人员的国际调查人员合作，并具有很强的记录东亚的大规模精神遗传研究。我们将创建可用于的最大的东亚队列发现新的MDD基因，增加遗传发现工作的多样性（迈向减少的一步健康差异），并进行详尽的分析，以确定MDD中可能的因果变异和基因。财团的目的如下：目标1：从韩国DNA样品和表型收集来自10,000名重复复发性MDD的妇女以及10,000名匹配，筛选的对照。我们将获得一个全面的临床特征和风险因素集，这是一系列深层的表型，这些表型提供了强大的资源用于基因鉴定。 AIM 2：我们将基因型样本，在韩国样本中绘制MDD的风险基因座，确定异质性的来源并检查基因和环境如何相互作用以引起MDD。目标3：识别东亚人群荟萃分析中MDD的遗传基因座，并且可能有一组因果变异通过在不同种族的人群中使用反式精细映射。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Predictors of diagnostic conversion from major depression to bipolar disorder: a Swedish national longitudinal study.

DOI：
10.1017/s0033291723001848
发表时间：
2023-12
期刊：
PSYCHOLOGICAL MEDICINE
影响因子：
6.9
作者：
Rhee, Sang Jin;Ohlsson, Henrik;Sundquist, Jan;Sundquist, Kristina;Kendler, Kenneth S.
通讯作者：
Kendler, Kenneth S.