Circulation Research Thematic Synopsis

Abstract

Circulation Research Thematic Synopses:The goal of Thematic Synopses is to provide our readers with a concise but comprehensive overview of the work published in Circulation Research, which we hope will keep our readers abreast of recent scientific discoveries and facilitate discussion, interpretation, and integration of the findings. These collections of articles are organized thematically and the papers listed in chronological order, beginning with the most recent ones. In each synopsis, the top ten downloaded original research articles (normalized to time since publication) are highlighted in yellow. Review articles are also included with titles highlighted in blue and the summary of each is provided. Instead of using abstracts, we have elected to publish the Novelty and Significance section of each article, which we believe provides a clear précis of the salient findings and their implications in a language that is easily understandable by the non-initiated. This will enable readers who are not experts in a particular field to grasp the significance and impact of work performed in other fields. It is our hope and expectation that Thematic Synopses will help readers to gain a broader awareness and a deeper understanding of the status of research across the vast landscape of cardiovascular research. -The Editors Circulation Research Thematic Synopsis Cardiovascular GeneticsThe Editors I n the recent past, the landscape of human molecular genetics has changed dramatically. The conventional approach was to gain insight into the genetic basis of human diseases by linkage analysis of large families with Mendelian patterns of inheritance. This approach has been all but replaced by newer approaches of genome-wide association studies (GWAS) and next-generation DNA sequencing. 1 The utility of genetic linkage analysis in deciphering the molecular basis of single gene disorders is undeniable, and this approach has led to the elucidation of the genetic basis of many monogenic disorders. [2][3][4][5][6] Likewise, genetic linkage studies of rare forms of common diseases, wherein the phenotype exhibits a Mendelian pattern of inheritance, have provided significant insights into the molecular pathogenesis of common disorders. 7 The Achilles heel of the genetic linkage analysis, however, is the small family, because the family size and structure do not afford sufficient power to assess cosegregation of the phenotype with allele inheritance. Linkage analysis also is not applicable to sporadic cases and, therefore, to common complex disorders, which seldom exhibit Mendelian patterns of inheritance. 8 As a result, despite the success in elucidating the genetic basis of many monogenic disorders, the genetic basis of common complex diseases and also sporadic or small family single gene disorders has remained largely unknown.The advent of high-throughput genotyping tools, such as high-density gene chips or arrays, ushered in the era of GWAS. This afforded new opportunities for identifying susceptibility alleles for common diseases ...