Genetic determinants of coronary artery calcification progression in the Heinz Nixdorf Recall Study: A Genome-wide association study

Heinz Nixdorf Recall 研究中冠状动脉钙化进展的遗传决定因素：全基因组关联研究

• 批准号: 278740940
• 负责人: Dr. Sonali Pechlivanis, Ph.D.
• 金额: --
• 依托单位: Institut für Medizinische Informatik, Biometrie und Epidemiologie (IMIBE)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/278740940?language=en
• 关键词: Genetic; determinants; coronary; artery; calcification

Atherosclerosis is the primary cause of coronary artery disease (CAD) and precedes the onset of most cases of clinically apparent coronary heart disease (CHD) by decades. Coronary artery calcification (CAC) is one of the most sensitive and specific markers of coronary atherosclerotic. The heritability of CAC progression has been reported to be strong, accounting for around 40% of the observed variance with 14% of variation explained by genetic factors. However, the genetic factors that are associated with progression of CAC are almost unknown. The importance of genome-wide association study (GWAS) is highlighted by its success to identify and reproduce genetic loci associated with various diseases. In this study we propose to carry out a GWAS approach in 3,481 Heinz Nixdorf Recall participants to find genetic variants associated with progression of CAC. We will adopt a two-stage strategy (a) discovery phase and (b) validation phase. In the discovery phase we will screen 3,481 Heinz Nixdorf Recall participants using latest genotyping chips to find signals associated with progression of CAC during a 5-year follow-up period. In the validation phase we will validate the top significant signals (up to 1000 markers selected based on P-values) in independent samples from NELSON Study. The proposed study will help to identify and validate genetic variants affecting progression of CAC which may help explain the essential mechanisms leading to CAD and might aid development of strategies to prevent, predict and treat CAD.

动脉粥样硬化是冠状动脉疾病（CAD）的主要原因，并且在大多数临床上明显的冠心病（CHD）病例的发病之前数十年。冠状动脉钙化（CAC）是冠状动脉粥样硬化最敏感、最特异的标志物之一。据报道，CAC进展的遗传力很强，约占观察到的变异的40%，其中14%的变异由遗传因素解释。然而，与CAC进展相关的遗传因素几乎未知。全基因组关联研究（GWAS）的重要性在于它成功地识别和复制了与各种疾病相关的遗传位点。在这项研究中，我们建议在3，481名海因茨Nixdorf召回参与者中进行GWAS方法，以发现与CAC进展相关的遗传变异。我们将采用两阶段策略（a）发现阶段和（B）验证阶段。在发现阶段，我们将使用最新的基因分型芯片筛选3，481名海因茨Nixdorf Recall参与者，以在5年随访期间发现与CAC进展相关的信号。在验证阶段，我们将验证来自纳尔逊研究的独立样本中最显著的信号（基于P值选择的多达1000个标记物）。这项拟议的研究将有助于识别和验证影响CAC进展的遗传变异，这可能有助于解释导致CAD的基本机制，并可能有助于制定预防，预测和治疗CAD的策略。