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遗传独立的注意力缺陷/多动症（ADHD），这将最好单独研究。我们还确定了对注意力问题的高度遗传责任。这种新应用的远程目标是鉴定遗传因素，这些因素易受着严重注意力问题的发展。本应用的具体目标是使用定量性状基因座（QTL）完成整个基因组链接研究和候选基因分析，以及组合连续特征和分类表型定义的多元方差组件分析。目标样本是澳大利亚的家族，这些家族已经被发现和特征在不关注意问题（天鹅量表和DSM-IV ADHD症状）中。这种双胞胎家族的样本似乎代表了澳大利亚一般人口，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，这种方法通常不会引起临床关注。我们将使用新型的表型方法，包括对不集中的连续评估（天鹅量表）和潜在级别定义的ADHD亚型。由于已经收集了两种关键表型的数据，因此我们将有效地选择具有最大功能的1,200个家庭，以检测7,550个家庭的样本中的联系或关联。我们预计有1,000个家庭的完整数据（都是父母，每个家庭平均4个兄弟姐妹）。该样品将完成整个基因组10cm扫描，对15个有据可查的候选基因（包括DRD4，DRD5，DAT，SNAP-25和CHRNA4基因）的单核苷酸多态性（SNP）分析。这种合并的方法将确定候选基因与基于人群的家庭样本中的不集中形式的多动症的相关性，并具有足够的能力，可以发现与不集中ADHD相关的新染色体位置。此外，使用现有的家庭流行病学样本1）对特定基因与普通人群的相关性进行有力测试，2）具有足够的能力，可以发现与无关紧要的ADHD相关的新基因座，3）3）3）将避免使用ADHD案例的基于临床或广告的其他研究的其他研究的其他潜在研究的潜在研究，以及与一般性相关的研究范围，以及一般性的使用范围。由于使用现有良好的样本以及澳大利亚和美国研究人员之间的合作研究的悠久历史，这将是可观的成本节省。