Endophenotypes for Molecular Genetic Studies of ADHD

ADHD 分子遗传学研究的内表型

• 批准号: 6836223
• 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/6836223
• 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最复杂的，并且是几种小作用基因之间相互作用的结果。因此，有必要开发与基因作用密切相关的表型数据，以检测其作用。假设代表给定疾病的遗传责任的生物学标记物称为“内型型”，可能会提供有助于识别此类基因的表型数据。持续关注和执行功能措施的表现很大程度上取决于涉及前额叶皮层的神经回路，因为鉴于被诊断出患有这种疾病的儿童经常在此类措施上表现出缺陷，因此可能代表多动症的内型型。当前建议的目的是开始制定一项研究计划，以评估持续的关注和执行功能措施作为多动症的内型型。该研究计划将着重于评估这些措施的心理测量特性（可靠性，内部有效性和外部有效性），使用单变量和多元行为遗传分析的这些措施的表现在这些措施上的绩效以及这些度量能够复制ADHD和选择候选候选基因之间的相关和联系的证据的能力。