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

项目摘要/摘要 性少数群体(SM，即非异性恋者)和性别少数群体(GM，即有 与出生时被分配的性别不一致的性别，而不是具有 与出生时分配的性别一致的性别)人(统称为SGM) 面临着更大的健康差距风险，包括非常高的药物使用率。在关于物质使用的研究中， 由于转基因地位很少得到衡量或报告，转基因人士在很大程度上没有代表。主要的解释是 SGM人群中较高的药物使用率和健康问题是少数人的压力，这赋予了 对SGM人的额外压力负担，包括歧视经历、对歧视的期望、 隐藏自己的身份，内化社会污名。表观遗传修饰(例如，DNA 甲基化)是跟踪对物质使用和少数应激反应的分子修饰的一种方式。 了解物质使用和少数民族压力的表观遗传学可能有助于我们开发更好的方法来 识别和治疗物质使用障碍，并了解SGM人群下游的健康结果。 这项研究将利用Pride研究，这是一项对SGM人群进行的全国性纵向队列研究，以确定 SGM人群在超过3年的年度数据收集中的物质使用轨迹(N&GT；3937岁，18岁)， 检查GM和顺性SM人群在这些轨迹上的差异，并检查关系 少数应激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，其中一半是转基因)之间的差异 GM与顺性SM人群物质使用与DNA甲基化的关系 DNA甲基化和物质使用之间的这些关系中的哪一个即使在考虑到 少数压力(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人员向有针对性的预防和干预发展提供信息。这项研究还将向 开发药物使用的生物标志物，以改善药物使用的治疗和预防。

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.