Molecular Genetics of Inattention in Australia

澳大利亚注意力不集中的分子遗传学

• 批准号: 7474701
• 负责人: THEODORE J CICERO
• 金额: $ 40.62万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-25 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7474701
• 关键词: Advertisements; Affect; Arts; Attention; Attention deficit hyperactivity disorder; Australia; Candidate Disease Gene; Class; Clinic; Clinical; Communities; Complex; Cost Savings; DRD4 gene; DRD5 gene; DSM-IV; Data; Detection; Development; Diagnosis; Diagnostic; Dimensions; Disease; Employment; Etiology; Family; Family Study; Frequencies; General Population; Genes; Genetic; Genome; Genome Scan; Genomics; Genotype; Goals; Haplotypes; Health; Joints; Laboratories; Link; Location; Measures; Medical Research; Methods; Missouri; Modeling; Molecular Genetics; Mutation; Numbers; Other Genetics; Parents; Phenotype; Polymorphism Analysis; Population; Positioning Attribute; Predisposing Factor; Quantitative Trait Loci; Range; Recording of previous events; Recruitment Activity; Research Personnel; Sampling; Sampling Biases; Scanning; Screening procedure; Siblings; Single Nucleotide Polymorphism; Social Problems; Surveys; Symptoms; Techniques; Testing; Twin Multiple Birth; Twin Studies; United States; United States National Institutes of Health; base; design; disorder subtype; genetic element; genetic linkage; genetic linkage analysis; inattention; instrument; novel; trait

DESCRIPTION (provided by applicant): Our recent studies have demonstrated the presence of multiple, genetically independent forms of attention deficit/hyperactivity disorder (ADHD) which would be best studied individually. We have also identified a highly heritable continuum of Liability to attention problems. The long-range goal of this new application is the identification of genetic factors that predispose to the development of severe inattention problems. The specific goals of this application are to complete a whole genome linkage study and candidate gene analyses using quantitative trait locus (QTL) as well as multivariate variance components analyses of combined continuous trait and categorical phenotype definitions. The target sample is families in Australia that have already been identified and characterized for inattention problems (SWAN scale and DSM-IV ADHD symptoms). This sample of twin families appears representative of the general population of Australia and, hence, represents a community-based approach to studying this form of ADHD, which frequently does not come to clinical attention. We will use novel phenotyping approaches including a continuum assessment of inattention (the SWAN scale) and latent-class defined ADHD subtypes. Because data on the two key phenotypes have already been collected, we will be in a position to efficiently select the 1,200 families with greatest power to detect linkage or association out of the existing sample of 7,550 families. We anticipate having complete data on 1,000 of these families (both parents and an average of 4 siblings per family). A whole genome 10cM scan will be completed on this sample as will single nucleotide polymorphism (SNP) analysis of 15 well-documented candidate genes (including the DRD4, DRD5, DAT, SNAP-25 and CHRNA4 genes). This combined approach will determine the relevance of candidate genes to inattentive forms of ADHD in a population-based sample of families as well as have sufficient power to discover new chromosomal locations linked to inattentive ADHD. Furthermore, using an existing epidemiological sample of families will 1) provide a powerful test of the relevance of specific genes to the general population, 2) have sufficient power to discover new loci related to inattentive ADHD, 3) will avoid many of the potential confounds of other studies using clinic or advertisement-based sampling of ADHD cases, and 4) will test the general relevance of findings from the United States by the use of an independent and culturally diverse sample. This will be at a marked cost savings due to the employment of existing well-characterized samples and the long history of collaborative studies between investigators from Australia and the United States.

描述（由申请人提供）：我们最近的研究表明存在多种与遗传无关的注意力缺陷/多动障碍（ADHD）形式，最好单独研究。我们还发现了注意力问题的高度遗传性连续体。这项新应用的长期目标是识别容易导致严重注意力不集中问题的遗传因素。该应用程序的具体目标是使用数量性状位点（QTL）完成全基因组连锁研究和候选基因分析，以及组合连续性状和分类表型定义的多变量方差成分分析。目标样本是已经被识别和描述为注意力不集中问题（SWAN 量表和 DSM-IV ADHD 症状）的澳大利亚家庭。这个双胞胎家庭样本似乎代表了澳大利亚的一般人群，因此代表了一种基于社区的方法来研究这种形式的多动症，这种形式通常不会引起临床关注。我们将使用新颖的表型分析方法，包括注意力不集中的连续评估（SWAN 量表）和潜在类别定义的 ADHD 亚型。由于两个关键表型的数据已经收集，我们将能够从现有的 7,550 个家族样本中有效地选择最有能力检测连锁或关联的 1,200 个家族。我们预计将获得其中 1,000 个家庭的完整数据（父母双方以及每个家庭平均 4 个兄弟姐妹）。对此样本将完成全基因组 10cM 扫描，并对 15 个有据可查的候选基因（包括 DRD4、DRD5、DAT、SNAP-25 和 CHRNA4 基因）进行单核苷酸多态性 (SNP) 分析。这种组合方法将在基于人群的家庭样本中确定候选基因与注意力不集中型多动症的相关性，并有足够的能力发现与注意力不集中型多动症相关的新染色体位置。此外，使用现有的家庭流行病学样本将 1) 提供对特定基因与一般人群的相关性的有力测试，2) 有足够的能力发现与注意力不集中的 ADHD 相关的新基因座，3) 将避免许多潜在的混淆使用临床或基于广告的 ADHD 病例抽样进行的其他研究，4) 将通过使用独立且文化多样化的样本来测试来自美国的研究结果的一般相关性。由于使用现有的特征良好的样本以及澳大利亚和美国研究人员之间长期合作研究的历史，这将显着节省成本。