Endophenotypes for Molecular Genetic Studies of ADHD

ADHD 分子遗传学研究的内表型

• 批准号: 6927052
• 负责人: IAN ROBERT GIZER
• 金额: $ 2.52万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2007-08-23
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6927052
• 关键词: adolescence (12-20); attention; attention deficit disorder; behavioral /social science research tag; behavioral genetics; clinical research; disease /disorder classification; disease /disorder etiology; dopamine receptor; dopamine transporter; functional ability; gene environment interaction; genetic markers; genetic susceptibility; human data; human genetic material tag; human subject; middle childhood (6-11); phenotype; predoctoral investigator; psychometrics; questionnaires; statistics /biometry; twin /multiplet

The genetic influences that contribute to psychiatric disorders are most often complex, and are the result of interactions between several genes of small effect. Thus, it is necessary to develop phenotypic data that is as closely related to the action of the gene as is possible in order to detect their effect. Biological markers hypothesized to represent genetic liability to a given disorder, termed "endophenotypes", may provide phenotypic data useful in identifying such genes. Performance on sustained attention and executive functions measures, thought to depend heavily on neural circuits involving the prefrontal cortex, might represent an endophenotype for ADHD given that children diagnosed with this disorder often show deficits on such measures. The purpose of the current proposal is to begin developing a research program for evaluating sustained attention and executive functions measures as endophenotypes for ADHD. This research program will focus on evaluating the psychometric properties of these measures (reliability, internal validity, and external validity), the extent to which performance on these measures is heritable using univariate and multivariate behavior genetic analyses, and the ability of these measures to replicate previously observed evidence of association and linkage between ADHD and selected candidate genes.

导致精神疾病的遗传影响通常是复杂的，是几个影响较小的基因之间相互作用的结果。因此，有必要开发尽可能与基因作用密切相关的表型数据，以检测其作用。被假设为代表对给定疾病的遗传易感性的生物标记物，称为“内表型”，可以提供用于鉴定这些基因的表型数据。持续注意力和执行功能的表现，被认为在很大程度上取决于涉及前额叶皮层的神经回路，可能代表ADHD的一种内表型，因为诊断患有这种疾病的儿童经常在这些措施上表现出缺陷。目前的建议的目的是开始发展一个研究计划，以评估持续的注意力和执行功能的措施，为多动症的内表型。该研究计划将重点评估这些措施的心理测量特性（可靠性，内部效度和外部效度），在何种程度上这些措施的性能是遗传使用单变量和多变量行为遗传分析，以及这些措施的能力，复制先前观察到的证据之间的关联和联系ADHD和选定的候选基因。