Genetic comorbidity for disordered eating, alcohol use, and personality

描述(申请人提供)：饮食失调特征是指可能导致更多危及生命的疾病发展的饮食态度和行为，如饮食失调。通常被称为进食病理，进食特征紊乱和进食障碍是遗传和环境因素共同作用的结果。虽然饮食病理通常与饮酒和特定的个性特征共同发生，但对遗传和环境因素对这种关系的影响还没有得到仔细的研究。一个特定的候选基因可能在某些个性特征的个体差异中发挥作用，以及对酒精使用障碍和饮食病理的易感性，是5-羟色胺转运体基因(SLC6A4)。初步结果令人振奋，表明该基因的多态与饮食病理之间存在关联，但需要对这些发现进行独立的复制。此外，SLC6A4基因的多态被假设为解释饮食病理、饮酒和个性之间的关系，但还没有研究直接评估这一假设。利用现有的数据，本研究将进行二次分析，以1)调查进食障碍、饮酒和个性之间的遗传和环境关系，2)利用密集的多态图谱来检查进食障碍与SLC6A4多个多态的关联，以及3)分析SLC6A4的多态在多大程度上解释进食障碍、饮酒和某些人格特征之间的关系。参加科罗拉多州反社会药物依赖中心的青少年和年轻成年女性双胞胎及其女性非双胞胎兄弟姐妹将被纳入这些分析。首先，生物计量模型拟合将被用来在单变量和多变量水平上评估遗传和环境对这些特征的影响。此外，将使用最先进的统计程序包，允许对候选基因进行适当的分析，特别是在考虑到多种表型的情况下。具体地说，这项研究将研究SLC6A4基因的多个多态与饮食失调的关系。在某种程度上，这些多发性症状与饮食失调有关，我们将对它们进行检查，同时也会考虑到饮酒和个性特征。识别进食障碍和相关行为的生物标志物(即基因)不仅将为现有的关于这些行为之间的关系的知识增加重要信息，而且还可能阐明药物治疗在改变这些症状方面可能发挥的作用。及早识别可能共享相似风险因素的多种行为特征之间的关系非常重要，这可能会潜在地防止更有害行为的出现。

DESCRIPTION (provided by applicant): Disordered eating characteristics are eating attitudes and behaviors that may lead to the development of more life-threatening illnesses, such as eating disorders. Often referred to as eating pathology, disordered eating characteristics and eating disorders result from a combination of genetic and environmental factors. Although eating pathology commonly co-occurs with alcohol use and particular personality traits, understanding genetic and environmental contributions to this relationship has not been closely examined. One specific candidate gene that may play a role in individual differences in certain personality traits, as well as vulnerability to alcohol use disorder and eating pathology, is the serotonin transporter gene (SLC6A4). Initial results are promising, suggesting associations between polymorphisms in this gene and eating pathology, but independent replications of these findings are needed. Moreover, polymorphisms in SLC6A4 have been hypothesized to explain relationships among eating pathology, alcohol use, and personality, yet no study has directly assessed this hypothesis. Using existing data, this study will conduct secondary analyses to 1) investigate genetic and environmental relationships among disordered eating, alcohol use, and personality, 2) utilize a dense polymorphism map to examine associations of disordered eating with multiple polymorphisms in SLC6A4, and 3) analyze the extent to which polymorphisms in SLC6A4 explain relationships among disordered eating, alcohol use, and certain personality traits. Adolescent and young adult female twins and their female non-twin siblings participating in the Colorado Center for Antisocial Drug Dependence will be included in these analyses. Initially, biometrical model fitting will be used to assess genetic and environmental influences on these characteristics at both the univariate and multivariate levels. In addition, state-of-the-art statistical packages will be used that allow for appropriate analyses of candidate genes, especially when taking into account multiple phenotypes. Specifically, this study will look at associations between multiple polymorphisms in SLC6A4 with disordered eating. To the extent that these polymoprhisms are related to disordered eating, they will be examined while also taking into account alcohol use and personality traits. Identifying biological markers (i.e., genes) of disordered eating and related behaviors will not only add significant information to existing knowledge about what contributes to relationships among these behaviors, but may also shed light on the role pharmacological treatments may have in modifying these symptoms. The importance of identifying relationships among multiple behavioral characteristics that may share similar risk factors early on could potentially prevent the emergence of more harmful behaviors.