Genomewide Association Study of Conotruncal Heart Disease

圆锥动脉心脏病全基因组关联研究

• 批准号: 7773073
• 负责人: Elizabeth Goldmuntz
• 金额: $ 24.29万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-15 至 2012-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7773073
• 关键词: Accounting; Affect; Anatomy; Animals; Applications Grants; Cardiac; Child; Cleaved cell; Clinical; Complex; Congenital Abnormality; Congenital Heart Defects; Data; Data Set; Development; Disease; Epidemiology; Face; Family; Genes; Genetic; Genetic Variation; Genotype; Hand; Health; Heart Diseases; Human; Individual; Inherited; Investigation; Longevity; Methods; Morbidity - disease rate; Neural Tube Defects; Outcome; Parents; Pathway interactions; Phenotype; Primary Prevention; Public Health; Research; Research Project Grants; Risk; Risk Factors; SNP genotyping; Societies; Subgroup; Triad Acrylic Resin; Work; falls; genetic variant; genome wide association study; genome-wide; innovation; interest; malformation; mortality; novel; programs; public health relevance; tool

DESCRIPTION (provided by applicant): Malformations of the heart are the most common, serious birth defects, and an important cause of morbidity and mortality throughout the lifespan of affected individuals. Despite the public health significance of these conditions, the causes of congenital heart defects are poorly understood and primary prevention methods are lacking. Like other structural malformations, such as neural tube defects and facial clefts, most non-syndromic cases of CHDs are thought to be genetically complex conditions determined by the effects of multiple environmental and genetic factors. However, there are few established risk factors for non-syndromic CHDs in general, or for subgroups such as the CTDs. This situation is not unlike that for several other common, complex diseases, for which recent genome-wide association studies (GWAS) have provided strong evidence for the existence of common, disease-related, gene variants. Hence, application of genome-wide approaches to the study of CHDs is of extreme interest and has the potential to significantly advance our understanding of the pathways that are involved in the development of these conditions. We propose to perform the statistical analyses required to complete a GWAS of a subgroup of CHDs referred to as conotruncal heart defects (CTDs). This subgroup accounts for approximately 1/3rd of all CHDs, and there is a substantial body of data, derived from both animal and human studies, indicating that the cardiac phenotypes that fall within it are more closely related to each other than to other forms of CHDs. Through the ongoing efforts of this research team, SNP genotyping data from the Illumina 550K chip for 800 CTD case-parent triads are in hand and awaiting analyses to: (1) Identify maternal and inherited (i.e. case) genotypes that are associated with CTDs, and (2) Identify pathways and gene sets that are associated with CTDs. PUBLIC HEALTH RELEVANCE: Conotruncal heart defects are common, serious malformations of the heart that have a significant impact on affected individuals, their families and society. Despite the health significance of these conditions, the causes of conotruncal heart defects are poorly understood and primary prevention methods are lacking. The work proposed in this application will help to indentify genes that are associated with the risk that a child will be born with one of these conditions.

描述（由申请人提供）：心脏畸形是最常见、最严重的出生缺陷，也是受影响个体整个生命周期内发病和死亡的重要原因。尽管这些疾病的公共卫生意义，先天性心脏病的原因知之甚少，缺乏一级预防方法。像其他结构性畸形，如神经管缺陷和面部裂缝，大多数非综合征的CHD病例被认为是由多种环境和遗传因素的影响决定的遗传复杂条件。然而，对于非综合征型CHD或CTD等亚组，几乎没有确定的风险因素。这种情况与其他几种常见的复杂疾病没有什么不同，最近的全基因组关联研究（GWAS）为常见的疾病相关基因变异的存在提供了强有力的证据。因此，应用全基因组方法来研究CHD是非常有意义的，并且有可能显着提高我们对参与这些条件发展的途径的理解。我们建议进行所需的统计分析，以完成一个被称为圆锥动脉干心脏缺陷（CTD）的CHD亚组的GWAS。该亚组约占所有CHD的1/3，并且有大量来自动物和人体研究的数据表明，与其他形式的CHD相比，属于该亚组的心脏表型彼此之间的关系更密切。通过该研究团队的持续努力，来自Illumina 550 K芯片的800个CTD病例-父母三联体的SNP基因分型数据正在等待分析：（1）确定与CTD相关的母体和遗传（即病例）基因型，以及（2）确定与CTD相关的途径和基因集。 公共卫生关系：圆锥动脉干心脏缺陷是常见的严重心脏畸形，对受影响的个人，他们的家庭和社会有重大影响。尽管这些疾病的健康意义，圆锥动脉干心脏缺陷的原因知之甚少，缺乏一级预防方法。本申请中提出的工作将有助于识别与儿童出生时患有这些疾病之一的风险相关的基因。