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: 10703685
• 负责人: Annesa Flentje
• 金额: $ 9.17万
• 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/10703685
• 关键词: Abstinence; Accounting; American; 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; Incidence; Infection; Injury; Investigation; Lesbian Gay Bisexual Transgender Queer; Longitudinal Studies; Longitudinal cohort; Longitudinal cohort study; Malignant Neoplasms; Measurement; Measures; Mental disorders; Methylation; Modification; Molecular; National Institute of Drug Abuse; Nature; Outcome; Pattern; Persons; Population; Prevention; 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; gender minority group; health disparity; immune function; improved; internalized stigma; male; maltreatment; men; methylome; minority stress; minority stressor; perceived discrimination; prevent; respiratory; response; sex; sexual minority; social stigma; substance use; substance use treatment; therapy development; traumatic stress

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.

项目概要/摘要 性少数群体（SM，即非异性恋者）和性别少数群体（GM，即有性倾向的人） 性别与出生时指定的性别不一致，而不是顺性别者 与出生时指定的性别一致的人（统称为 SGM）是 面临更大的健康差异风险，包括极高的物质使用率。在物质使用研究中， 由于很少衡量或报告 GM 状况，因此 GM 人员基本上没有代表性。主要解释为 SGM 人中药物滥用和健康问题的比例较高是少数群体的压力，这赋予了 SGM人的额外压力负担包括歧视经历、歧视预期、 隐藏个人身份，以及社会耻辱的内在化。表观遗传修饰（例如 DNA 甲基化）是追踪响应物质使用和少数族裔压力的分子修饰的一种方法。 了解物质使用和少数群体压力的表观遗传学可能有助于我们开发更好的方法 识别和治疗物质使用障碍，并了解 SGM 人员的下游健康结果。 这项研究将利用 PRIDE 研究（一项针对 SGM 人员的全国纵向队列研究）来确定 SGM 人员在 3 年的年度数据收集中的物质使用轨迹（N > 3937 岁 18 岁以上）， 检查 GM 与顺性别 SM 人在这些轨迹上的差异，并检查关系 少数群体压力与物质使用轨迹之间的关系（目标 1）。这项研究将确定这些关系 物质使用轨迹和 DNA 甲基化（N=600，其中一半是 GM）之间的差异，确定 GM 与顺性别 SM 人群的物质使用和 DNA 甲基化之间的关系，并确定 DNA 甲基化和物质使用之间的哪些关系即使在考虑了以下因素后仍然存在： 少数群体压力（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 GM 人员为有针对性的预防和干预措施的制定提供信息。这项研究还将告知 开发物质使用的生物标志物，以改善物质使用的治疗和预防。