The Genetics of Co-occurring Alcohol Use and Self-Harm

描述（由申请人提供）：这个独立的博士后奖学金（F32）的目的是支持申请人的培训目标，提高对酒精参与的遗传学及其与自我伤害和其他形式的精神病理学（例如，边缘型人格障碍），同时促进了复杂双胞胎建模和分子遗传学方法的专业知识。先前的研究表明，报告有问题的酒精参与的青少年和成年人更有可能进行自我伤害，包括自杀企图（SA）和非自杀性自我伤害（NSSI）。然而，关于可能导致自伤和酒精参与的各个阶段之间的共病的推定遗传因素，如早发性酒精使用和酒精使用障碍（AUD），相对知之甚少。本研究的目的是利用遗传信息双胞胎和全基因组关联研究（GWAS）数据集，以检查酒精参与，NSSI和SA之间的遗传重叠，并检查边缘性人格特征（BPF）对这种共病的影响。具体目的是（1）检查自我伤害和早发性酒精使用之间的关系，更具体地说，报告早发性酒精使用的个体是否更有可能报告自我伤害，以及遗传和个体特定环境影响将早期酒精暴露与自我伤害联系起来的程度，（2）检查自我伤害和AUD之间的关系，特别是遗传和环境因素在多大程度上将自伤与AUD联系起来，以及BPF对这种遗传和环境重叠的影响，最后，（3）确定基因组对自伤的影响，并调查它们是否有助于自伤与AUD的关系。在实现这些目标的同时，还将实现以下培训目标：（a）提高对酒精参与的遗传学及其与自我伤害的共病性的理解，（B）提高与双胞胎方法有关的技能，包括多变量双胞胎建模和不一致双胞胎方法，（c）获得基因组研究的技能，包括GWAS，（d）获得负责任的研究培训，（e）准备职业发展补助金。申请人组建了一个具有酒精相关措施遗传学专业知识的指导团队和在NSSI和BPF方面具有相当专业知识的顾问，并提出了一个将教学法（例如成瘾遗传学和基因组学的正式课程）与其指导团队一对一讨论相结合的培训计划。本提案的短期目标是编制出版物，作为拟订今后提案的初步数据。这项培训和研究的长期目标是将申请人确立为 他是一名独立的调查员，擅长酒精参与和精神病理学的生物学研究。

DESCRIPTION (provided by applicant): The objective of this independent postdoctoral fellowship award (F32) is to support the applicant's training goals of improving understanding of the genetics of alcohol involvement and its comorbidity with self-harm and other forms of psychopathology (e.g., borderline personality disorder), while facilitating expertise in statistica genetic methods, both complex twin modeling and molecular genetic approaches. Previous research has demonstrated that adolescents and adults reporting problematic alcohol involvement are much more likely to engage in self-harm, both suicidal attempt (SA) and non-suicidal self-injury (NSSI). Relatively little is known, however, about putative genetic factors tht may contribute to the comorbidity between self-harm and various stages of alcohol involvement, such as early onset alcohol use and alcohol use disorder (AUD). The aim of this investigation is to utilize genetically informative twin and genomewide association study (GWAS) datasets to examine the genetic overlap between alcohol involvement, NSSI and SA, and to also examine the influence of borderline personality features (BPF) on this comorbidity. The specific aims are (1) to examine the relationship between self-harm and early onset alcohol use, more specifically, whether individuals reporting early onset alcohol use are more likely to report self-harm and the degree to which genetic and individual-specific environmental influences link early alcohol exposure to self-harm, (2) to examine the relationship between self- harm and AUD, specifically the extent to which genetic and environmental factors link self-harm and AUD and the influence of BPF on this genetic and environmental overlap, and finally, (3) to identify genomic influences on self-harm and investigate whether they contribute to its relationship with AUD. Accomplishing these aims will be accompanied by the following training objectives: (a) improve understanding of the genetics of alcohol involvement and its comorbidity with self-harm, (b) enhance skills related to twin methodology, including multivariate twin modeling and the discordant twin approach, (c) acquire skills for genomic studies, including GWAS, (d) obtain responsible conduct of research training, and (e) prepare a career development grant. The applicant has assembled a mentoring team with expertise in the genetics of alcohol-related measures and consultants with considerable expertise in NSSI and BPF and proposed a training plan that combines didactics (e.g. formal coursework in addiction genetics and genomics) and one-on-one discussions with her mentoring team. The short term goal of this proposal is to produce publications that will serve as preliminary data for the development of future proposals. The long term goal of this training and research is to establish the applicant as an independent investigator with expertise in biologically informed studies of alcohol involvement and psychopathology.