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Sex Chromosome GWAS of Post-Traumatic Stress Disorder (PTSD)

创伤后应激障碍 (PTSD) 性染色体 GWAS

基本信息

批准号：
10304019
负责人：
Laramie Duncan
金额：
$ 20.81万
依托单位：
STANFORD UNIVERSITY
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：
2021-07-19 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10304019
关键词：
Adult Anxiety Disorders Biological Budgets Chromosomes Collaborations Data Data Aggregation Development Diagnosis Disease Eating Disorders Etiology Familiarity Female Future Gender Genes Genetic Genetic Risk Genetic study Genotype Healthcare Heritability International Length Link Literature Mental Depression Mental disorders Meta-Analysis Methods Military Personnel Molecular Genetics Post-Traumatic Stress Disorders Prevalence Prevention Prevention strategy Procedures Protocols documentation Pseudoautosomal Region Psychiatry Reporting Resources Risk Sampling Sex Chromosomes Sex Differences Substance Use Disorder Testing Time Twin Studies United States Variant Woman Work X Chromosome Y Chromosome autism spectrum disorder base cost disorder risk genome wide association study genomic data male men novel psychiatric genomics public health relevance sex substance use success therapy development treatment strategy

项目摘要

Project summary The untreated burden of post-traumatic stress disorder (PTSD) in the United States is a massive contributor to healthcare budgets in both the civilian and military sectors, and better treatment and prevention methods are needed. One of the most powerful predictors of who will develop a particular psychiatric disorder – including PTSD – is sex/gender. Women are diagnosed with post-traumatic stress disorder (PTSD), depression, eating disorders, and certain anxiety disorders approximately two to three times as often as men. Conversely, males are up to four times more likely to be diagnosed with autism and substance use disorders. In psychiatry, there are few factors that reliably confer fold-change differences in risk, but sex differences are an exception. Remarkably, the reasons for sex differences in prevalence of PTSD and other disorders remain relatively unexplained. Large-scale genetic studies, such as genome-wide association studies (GWAS), have demonstrated genetic effects on PTSD and other psychiatric disorders. However, a notable gap in the literature is the omission of the X and Y chromosomes from nearly all major psychiatric GWAS. Here we propose sex chromosome GWAS of large representative PTSD samples as a critical first step towards the inclusion of sex chromosomes in all major psychiatric GWAS. Building upon our prior work leading analyses for international groups, we will implement robust pipelines for sex chromosome analyses, which will expand sex chromosome analysis to PTSD. This work will also provide the necessary analytic workflows and collaboration building for future sex chromosome GWAS of all major psychiatric disorders. The field is almost completely in the dark regarding sex-chromosome contributions to psychiatric disorders, and it is critical that we identify sex chromosome loci and test for disproportionate contributions of sex chromosomes to genetic risk for disorders like PTSD and depression, in order to discover novel clues about disease etiology. This work may help to explain well-known sex differences in prevalence of psychiatric disorders, and sex chromosome findings may prove critical for the development of treatment and preventative strategies for these debilitating and costly disorders.

项目总结