Bipolar affective disorder in a genetic isolate

双相情感障碍（BP），或躁狂抑郁症，是世界范围内致残和死亡的主要原因。其终生患病率约为1%，自杀风险约为20%。该障碍的特征是躁狂或轻躁狂和抑郁发作，出现的顺序不同，有或没有间歇。双胞胎、家庭和收养研究指出，强烈的遗传因素导致双相情感障碍的发展，遗传率约为80%。然而，事实证明，确定这种疾病的遗传基础极其困难，许多研究都没有提供明确的数据。缺乏令人信服的结果被解释为复杂的遗传机制和受影响家庭和种族群体之间的潜在差异的迹象。基因隔离的群体，即大多数个体来自少数创始人的群体，被认为在理解复杂疾病（如双相情感障碍）的遗传基础方面具有巨大潜力。在这样的人群中，受影响的受试者很可能具有相同的易感基因，这使得这些基因更容易识别。在过去的10年里，我们一直在研究双相情感障碍，并取得了非常有希望的结果。在这个项目中，我们建议通过收集更多受影响的家庭来进一步研究，确认目前的积极发现，并将搜索范围缩小到一个小区域，可能是单个基因。如果成功，这项研究将是一个重大突破，通过确定分子途径和疾病机制，将为情绪障碍的生物学基础提供有价值和普遍有效的信息。

Bipolar affective disorder (BP), or manic-depressive illness, is a major cause of disability and mortality worldwide. It has a lifetime prevalence of about 1% and suicide risk of about 20%. The disorder is characterised by episodes of mania or hypomania and depression, appearing in varying succession, with or without intermission. Twin, family, and adoptive studies point to a strong genetic component leading to the development of bipolar disorder, with a heritability of the order of 80%. Yet the identification of the genetic basis of the disease has proved exceedingly difficult, with numerous studies producing no definitive data. The lack of convincing results has been interpreted as an indication of complex genetic mechanisms and underlying differences between affected families and ethnic groups. Genetically isolated populations, where most individuals descend from a small number of founders, are believed to hold great potential for understanding the genetic basis of complex diseases, such as bipolar disorder. Affected subjects in such populations are likely to share the same predisposing genes, making these genes easier to identify. During the last 10 years, we have been involved in the study of bipolar disorder in one such population, with very promising results. In this project, we propose to take the research further by collecting more affected families, confirming the current positive findings and narrowing down the search to a small region, possibly a single gene. If successful, the study will be a major breakthrough which, by identifying a molecular pathway and disease mechanism, will contribute valuable and generally valid information on the biological basis of mood disorders.