Genetic Linkage Study of Depression and Anxiety Disorders in an Arab Kindred

项目概述：本申请的长期目标是成为一名专注于抑郁症、焦虑症和创伤后应激障碍（PTSO）的遗传和环境病因学的独立研究人员。更好地了解这些疾病的起源将有助于制定更有针对性的预防和治疗策略。这一目标与国家精神卫生研究所减轻精神障碍负担的使命是一致的。职业发展奖将建立在研究者在精神流行病学和应用统计学方面的强大背景上，以发展遗传流行病学和应用统计遗传学方面的专业知识。拟议研究的具体目的是对以色列北部一个村庄的阿拉伯贝都因人亲属进行抑郁症和焦虑症的遗传联系研究，以确定影响其发展的基因。这个家族有很高的自杀率、抑郁症和焦虑症（分别为12%、30%和36%）。这种亲缘也是高度同质的，起源于一个创始人，并且具有很高的内婚率，这使得它成为鉴定影响这些表型的基因的独特和有希望的。我们还将对神经质进行连锁分析，神经质是一种涉及情绪反应的人格特质，作为一种定量的内表型，可能代表基因和表型之间的一种中间表达形式。作为一个探索性目的，我们将进行创伤后应激障碍的连锁分析，并研究基因和压力生活事件之间的相互作用对抑郁和创伤后应激障碍的影响。相关性：美国近50%的人口至少患有一种精神健康障碍。抑郁症和焦虑症是最常见的，因此构成了一个重大的公共卫生问题。这项提议的研究将使我们能够识别与抑郁症和焦虑症相关的基因，并将极大地提高我们识别高风险受试者和开发这些疾病治疗方法的能力。

DESCRIPTION (provided by applicant): Project Summary: The long-term objective of this application is to develop a career as an independent researcher focusing on the genetic and environmental etiology of depression, anxiety disorders, and posttraumatic stress disorder (PTSO). A better understanding of the genesis of these disorders would help develop more targeted prevention and treatment strategies. This objective is consistent with the National Institute of Mental Health's mission to reduce the burden of mental disorders. The career development award will build on the investigator's strong background in psychiatric epidemiology and applied statistics to develop expertise in genetic epidemiology and applied statistical genetics. The specific aims of the proposed research study are to conduct a genetic linkage study of depression and anxiety disorders to identify genes that influence their development in an Arab Bedouin kindred in a village in Northern Israel. This kindred has high rates of suicide, depression, and anxiety disorders (12 percent, 30 percent, and 36 percent, respectively). This kindred is also highly homogeneous originating from one founder and has high rates of endogamy, which make it unique and promising for identifying genes influencing these phenotypes. We will also conduct linkage analysis of neuroticism, a personality trait referring to emotional reactivity, as a quantitative endophenotype that may represent an intermediate form of expression between genes and phenotypes. As an exploratory aim, we will conduct linkage analyses of PTSD and examine the interaction between genes and stressful life events in their influence on depression and PTSD. Relevance: Almost 50 percent of the population in the United States suffer from at least one mental health disorder. Depression and anxiety disorders are the most common and thus constitute a major public health problem. The proposed study will allow us to identify genes associated with depression and anxiety disorders and would greatly advance our ability to identify subjects at high risk and develop treatment for these disorders.