LOCI PREDISPOISNG TO ANXIETY DISORDERS

焦虑症的易感基因位点

• 批准号: 7600990
• 负责人: Robert C. Elston
• 金额: $ 0.51万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7600990
• 关键词: 4q31; 4q31-q32; Agoraphobia; American; Anti-Anxiety Agents; Anxiety Disorders; Chromosomes; Comorbidity; Complex; Computer Retrieval of Information on Scientific Projects Database; Data Set; Diagnosis; Disease regression; Family; Funding; Genetic; Genome Scan; Grant; Individual; Institution; Methods; Neuropeptide Y Receptor; Panic Disorder; Phenotype; Phobic anxiety disorder; Predisposition; Rattus; Receptor Gene; Research; Research Personnel; Resources; Sampling; Site; Social Phobia; Source; United States National Institutes of Health; affection; base; genetic linkage analysis; genetic pedigree; genome-wide linkage; novel strategies; proband; trait

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We conducted a 10 cM linkage autosomal genome scan in a set of 19 American extended pedigrees (219 subjects) ascertained through probands with panic disorder. Several anxiety disorders, including social phobia, agoraphobia, and simple phobias - in addition to panic disorder- segregate in these families. In previous analyses on this sample, linkage analyses were based separately on each of the individual categorical affection diagnoses. Considering the substantial comorbidity between anxiety disorders and their probable shared genetic liability, it is clear that this method discards a considerable amount of information. We proposed a new approach that considers panic disorder, simple phobia, social phobia, and agoraphobia as expressions of the same multivariate, putatively genetically influenced, trait. We applied the multipoint Haseman-Elston method, using the grades of membership generated from a fuzzy clustering of these phenotypes as the dependent variable in Haseman-Elston regression. One region on chromosome 4q31-q34 around marker D4S413 (multipoint and single-point nominal p-values <0.00001) showed strong evidence of linkage (genome-wide significant at p<0.05). The same region is known to be the site of a neuropeptide Y receptor gene NPY1R (4q31-q32) that was recently implicated in anxiolytic-like effects in rats. Our findings support the notion that the major anxiety disorders, including phobias and panic disorder, are complex traits that share at least one susceptibility locus. We are currently tying to replicate this finding in an independent dataset.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们对一组通过惊恐障碍先证者确定的19个美国扩展家系(219名受试者)进行了10 cM连锁常染色体基因组扫描。一些焦虑症，包括社交恐惧症、广场恐惧症和简单恐惧症--除了恐慌症之外--在这些家庭中是分开的。在以前对这个样本的分析中，连锁分析是单独基于每个个体类别情感诊断的。考虑到焦虑症和他们可能共有的遗传责任之间的实质性共病，很明显，这种方法丢弃了相当大量的信息。我们提出了一种新的方法，将惊恐障碍、简单恐惧症、社交恐惧症和广场恐惧症视为同一多变量的、可能受遗传影响的特征的表达。我们应用了多点Haseman-Elston方法，将这些表型的模糊聚类产生的隶属度等级作为Haseman-Elston回归的因变量。染色体4q31-q34上标记D4S413附近的一个区域(多点和单点标称p值&lt；0.00001)显示了连锁的强烈证据(全基因组显著。已知的同一区域是神经肽Y受体基因NPY1R(4q31-q32)的位置，该基因最近被认为与大鼠的抗焦虑作用有关。我们的发现支持这样一种观点，即包括恐惧症和恐慌症在内的主要焦虑症是至少有一个易感基因的复杂特征。我们目前正在努力将这一发现复制到一个独立的数据集中。