Departments of Medicine and Biochemistry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada.
Can J Cardiol. 2013 Jan;29(1):10-7. doi: 10.1016/j.cjca.2012.10.011. Epub 2012 Nov 28.
The spring of 2012 marked the fifth anniversary of the widespread appearance in the biomedical literature of genome-wide association studies (GWAS) of diseases of adulthood. Articles reporting GWAS results now regularly appear in dozens of general medicine and cardiology journals. As of August 2012, more than 1700 published GWAS have reported findings across a range of human diseases. Many of these reported new genetic determinants of cardiovascular disease, including coronary artery disease and its risk factors such as diabetes, dyslipidemia, and hypertension. Though GWAS reports follow a standard format, superficially they can appear intimidating to most nongeneticists, whom we suspect often skip over them. Considering the importance of GWAS in cardiovascular science and medicine, and because they show no signs of fading, it is important for cardiovascular medical personnel and scientists to understand GWAS fundamentals. In this article, we provide a roadmap for the nonexpert reader to navigate through GWAS of cardiovascular disease. We cover the basic essentials needed to understand GWAS: underlying theory, mechanics, analysis and display, interpretation, and relevance. Areas covered include the relationship between GWAS and standard epidemiologic study design, the concepts of DNA sequence variation and linkage disequilibrium, the particular statistical considerations in studies involving many independent variables and large sample sizes, the meaning and interpretation of Manhattan plots, and the biologic and clinical significance of GWAS-based discoveries. We conclude with comments about the limitations of GWAS and about what to look for in the "post-GWAS era."
2012 年春季标志着成年疾病的全基因组关联研究（GWAS）在生物医学文献中广泛出现的第五个年头。报告 GWAS 结果的文章现在定期出现在数十种普通医学和心脏病学杂志上。截至 2012 年 8 月，已有超过 1700 项已发表的 GWAS 报告了一系列人类疾病的发现。其中许多报告了心血管疾病的新遗传决定因素，包括冠心病及其危险因素，如糖尿病、血脂异常和高血压。尽管 GWAS 报告遵循标准格式，但对大多数非遗传学家来说，它们表面上可能令人生畏，我们怀疑他们经常跳过这些报告。考虑到 GWAS 在心血管科学和医学中的重要性，而且它们没有消失的迹象，心血管医疗人员和科学家了解 GWAS 的基础知识非常重要。在本文中，我们为非专业读者提供了一张路线图，帮助他们理解心血管疾病的 GWAS。我们涵盖了理解 GWAS 所需的基本要素：基础理论、机制、分析和显示、解释和相关性。涵盖的领域包括 GWAS 与标准流行病学研究设计之间的关系、DNA 序列变异和连锁不平衡的概念、涉及许多独立变量和大样本量的研究中的特殊统计考虑因素、曼哈顿图的含义和解释，以及基于 GWAS 的发现的生物学和临床意义。我们最后对 GWAS 的局限性以及在“后 GWAS 时代”中应该注意的问题发表了评论。
