Outline

  • Abstract
  • 1. Introduction
  • 2. in Retrospect: 10 years of Cad Gwas
  • 3. the Challenges Involved in Moving from Genetic Associations to Therapeutic Targets and Beyond
  • 4. Conclusion
  • Supplementary Material
  • Disclosure Statement
  • Funding
  • Footnotes
  • References

رئوس مطالب

  • چکیده
  • کلیدواژه ها
  • 1. مقدمه
  • 2. نگاه به گذشته : 10 سال CAD GWAS
  • 2.1 پایه گذاری برای GWAS
  • 2.2 از GWAS تک تا تحقیق مشترک در مقیاس بزرگ
  • 2.3 دانش گزارش شده توسط GWAS تا به امروز
  • 3. چالش های موجود در حرکت از ارتباطات ژنتیک به سمت اهداف درمانی و فراتر
  • 3.1 تفسیر ژن های عامل در لوکوس GWAS
  • 3.2 آنالیز شبکه
  • 3.3 روش های ژنتیکی سیستم ها در زمینه قلبی عروقی
  • 3.4 مطالعات تصادفی مندلی
  • 3.5 پتانسیل پزشکی دقیق در CAD
  • 4. نتیجه گیری
  • منابع

Abstract

In this review, we summarize current knowledge on the genetics of coronary artery disease, based on 10 years of genome-wide association studies. The discoveries began with individual studies using 200K single nucleotide polymorphism arrays and progressed to large-scale collaborative efforts, involving more than a 100 000 people and up to 40 Mio genetic variants. We discuss the challenges ahead, including those involved in identifying causal genes and deciphering the links between risk variants and disease pathology. We also describe novel insights into disease biology based on the findings of genome-wide association studies. Moreover, we discuss the potential for discovery of novel treatment targets through the integration of different layers of ‘omics’ data and the application of systems genetics approaches. Finally, we provide a brief outlook on the potential for precision medicine to be enhanced by genome-wide association study findings in the cardiovascular field.

Keywords: - - - -

Conclusions

The last decade of genomic research has led to the identification of 163 common genetic loci conferring modest risk for CAD and MI. It is foreseeable that more variants will be identified by increasing GWAS sample sizes. In addition, whole-exome and whole-genome sequencing studies have identified rare risk variants in families and large patient cohorts with stronger effects. Nevertheless, although only part of the heritable risk for CAD is yet explained, we have developed a much more comprehensive picture of the biology underlying the disease, and with increasing numbers of functional studies aiming to decipher the link between genetic variation and CAD, we will finally identify novel treatment targets, as exemplified by PCSK9, ANGPTL4, ANGPTL3, and GUCY1A1. Hence, the findings generated by CAD GWAS represent an excellent starting point for the development of individualized treatment strategies in the future.

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