Substance use and DNA methylation at the intersection of sex and gender

性别和性别交叉点的药物使用和 DNA 甲基化

• 批准号: 10062388
• 负责人: Annesa Flentje
• 金额: $ 53.28万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10062388
• 关键词: Abstinence; Accounting; Alcohol or Other Drugs use; Area; Biological; Biological Markers; Biological Process; Birth; Blood specimen; Cessation of life; Chronic; Chronic stress; Cohort Studies; Complex; DNA; DNA Methylation; Data; Data Collection; Discrimination; Epigenetic Process; Exposure to; Gender; Gene Expression; Genes; HIV; Health; Health behavior; Immune; Incidence; Injury; Investigation; Lesbian Gay Bisexual Transgender Queer; Longitudinal Studies; Longitudinal cohort; Longitudinal cohort study; Measurement; Measures; Mental Health; Methylation; Minority; Modification; Molecular; National Institute of Drug Abuse; Nature; Outcome; Pattern; Population; Prevention; Preventive Intervention; Prospective cohort study; Reporting; Research; Risk; Sampling; Sexual and Gender Minorities; Strategic Planning; Stress; Substance Use Disorder; Time; Tissue-Specific Gene Expression; Translating; United States; Work; aged; biomarker development; cisgender; cohort; comorbidity; disability; epigenetic regulation; epigenomics; expectation; experience; gender minority; health disparity; improved; male; maltreatment; men; methylome; prevent; respiratory; response; sex; sexual minority; social stigma; stressor; therapy development

PROJECT SUMMARY/ABSTRACT Sexual minority (SM, i.e., people who are not heterosexual) and gender minority (GM, i.e., people who have a gender that is discordant from the sex they were assigned at birth, as opposed to cisgender people who have a gender that is concordant with the sex they were assigned at birth) people (collectively abbreviated as SGM) are at greater risk for health disparities including very high rates of substance use. Within studies on substance use, GM people are largely unrepresented as GM status is rarely measured or reported. The primary explanation for the higher rates of substance use and health problems among SGM people is minority stress, which confers an additional stress burden on SGM people including experiences of discrimination, expectations of discrimination, concealment of one’s identity, and internalization of social stigma. Epigenetic modifications (e.g., DNA methylation) are one way to track molecular modifications in response to substance use and minority stress. Understanding the epigenetics of substance use and minority stress may help us to develop better ways to identify and treat substance use disorders and to understand the downstream health outcomes of SGM people. This study will leverage The PRIDE Study, a national longitudinal cohort study of SGM people to identify trajectories in substance use among SGM people over 3 years of annual data collection (N > 3937 aged 18+), examine differences in these trajectories for GM versus cisgender SM people, and examine relationships between minority stress and substance use trajectories (Aim 1). This study will then identify the relationships between substance use trajectories and DNA methylation (N=600, half of whom are GM), identify differences in the relationships between substance use and DNA methylation for GM versus cisgender SM people, and identify which of these relationships between DNA methylation and substance use persist even after accounting for minority stress (Aim 2). This study will help us to understand longitudinal trajectories of substance use among SM and GM people to inform targeted prevention and intervention development. This study will also inform the development of biomarkers for substance use to improve substance use treatment and prevention.

项目摘要/摘要 性少数民族（SM，即不是异性恋者）和性别少数群体（GM，即有一个有一个的人 与他们在出生时分配的性别不一的性别，而不是具有 与他们出生时分配的性别一致的性别）人（统称为SGM）是 健康差异的风险更大，包括非常高的物质使用率。在有关药物使用的研究中， 通用汽车人很少衡量或报告，大多数人没有代表性。主要解释 SGM人群中较高的药物使用率和健康问题的率是少数派压力，它承认 对SGM人员的额外压力Burnen，包括歧视经历，歧视期望， 隐瞒自己的身份和社会污名的内在化。表观遗传修饰（例如DNA 甲基化）是针对物质使用和少数胁迫跟踪分子修饰的一种方法。 了解物质使用和少数族裔压力的表观遗传学可能有助于我们开发更好的方法 识别和治疗药物使用障碍，并了解SGM人的下游健康结果。 这项研究将利用《骄傲研究》，这是一项针对SGM人的国家纵向队列研究 SGM人员在3年的年度数据收集中使用物质使用的轨迹（n> 3937年龄18岁以上）， 检查转基因与cisgender SM人的这些轨迹的差异，并检查关系 在少数族裔压力和物质使用轨迹之间（AIM 1）。然后，这项研究将确定关系 在物质使用轨迹和DNA甲基化之间（n = 600，其中一半是GM），确定了差异 用于GM与Cisgender SM人的物质使用与DNA甲基化之间的关系，并确定 即使在考虑到DNA甲基化和物质使用之间的哪些关系，即使在考虑到 少数派压力（目标2）。这项研究将帮助我们了解物质使用的纵向轨迹 SM和通用汽车人会为有针对性的预防和干预开发提供信息。这项研究还将告知 开发用于改善药物使用治疗和预防的物质使用的生物标志物。