权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Genetics of PTSD in African Ancestry Populations: Enhancing discovery by addressing inequality

非洲血统人群 PTSD 的遗传学：通过解决不平等问题加强发现

基本信息

批准号：
10750547
负责人：
Dickens Howard Akena
金额：
$ 179.95万
依托单位：
BROAD INSTITUTE, INC.
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-25 至 2028-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10750547
关键词：
Acceleration Address Africa African African ancestry Alleles Chromosome Mapping Copy Number Polymorphism Data Data Collection Disease Electronic Health Record Elements Enrollment Ensure Equity European ancestry Freezing Funding Future Generations Genes Genetic Genetic Databases Genetic Markers Genetic Research Genetic study Genome Genomics Goals Haplotypes Individual Inequality Inequity Institution Investments Kenya Linkage Disequilibrium Maps Measures Mental disorders Meta-Analysis National Institute of Mental Health Participant Performance Persons Population Population Heterogeneity Population Programs Post-Traumatic Stress Disorders Psychiatry Recontacts Research Research Personnel Resources Risk Sample Size Sampling Scientific Advances and Accomplishments Signal Transduction Single Nucleotide Polymorphism Strategic Planning Time Trauma Uganda Variant Work biobank causal variant cohort data integration electronic health data gene discovery genetic architecture genetic risk factor genome resource genome wide association study genome-wide genome-wide analysis health inequalities improved large scale data meetings multi-ethnic neuropsychiatry non-genomic novel therapeutics polygenic risk score psychiatric genomics rare variant risk prediction risk variant success treatment disparity working group

项目摘要

PROJECT SUMMARY / ABSTRACT The broad goal of this application is to advance PTSD genetic discovery and address inequity in PTSD genetics research by leveraging a partnership between the Psychiatric Genomics Consortium – Posttraumatic Stress Disorder Working Group (PGC-PTSD) and a network of African investigators, including the Neuropsychiatric Genetics in African Populations (NeuroGAP) program and the Ugandan Genome Resource (UGR). By the end of 2022, the PGC-PTSD will achieve the largest genetic mapping of PTSD to date based on multiethnic meta- analysis of > 1,280,000 samples, leading to 95 risk loci meeting genome-wide significance for PTSD. Beyond discovery, recent work on polygenic risk scores in PTSD shows the potential for the utility of these measures in research. This success is overshadowed, however, by the persistent underrepresentation of African populations in PTSD genetic research, which poses a challenge for both scientific advances in PTSD and global equity. African genomes are characterized by shorter haplotype blocks and contain almost a million more variants per individual than populations outside Africa. The lower correlation between genetic markers in African populations is also useful for fine- mapping disease-causing alleles. However, differences in the African genome also result in limited cross-population transferability of polygenic risk scores, and, by extension, poorer performance in uncharacterized populations such as those from Africa. There is significant risk that the recent advances in PTSD genetics will result in a widening of the massive research and treatment disparities for African populations. This inequity is particularly troubling given the disproportionately high burden of trauma and PTSD faced by African populations both in the US and on the African continent. Thus, data from African populations in genetic studies of PTSD are critical to generate a complete picture of genetic risk factors, identify potentially missing novel therapeutic signals garnered by studying all populations, and address growing health inequity. We propose addressing this inequity by accomplishing the following Specific Aims: (1) Expand the PGC–PTSD sample bank with over 27,000 cases and 112,000 controls from the African continent and diaspora to achieve a robust, well- powered sample size of over 190,000 participants (~39,000 cases, 151,000 controls) with African ancestry; (2) Integrate data across Africa and African diaspora and perform analyses to expand PTSD risk loci discovery; and (3) Leverage African ancestry populations to improve fine-mapping and gene prioritization and to reduce health inequality by improving PRS accuracy for PTSD in these populations. These aims are highly consistent with NIMH Strategic Plan Goal 1, Objective 1.2, Strategy 1.2.A “Discovering gene variances and other genomics elements that contribute to mental illnesses in diverse populations.”

项目摘要/摘要