testing for rare variant associations in complex diseases测试罕见变异协会在复杂疾病.pdfVIP

Asimit and Zeggini Genome Medicine 2011, 3:24 /content/3/4/24 R E S E A R C H H I G H L I G H T Testing for rare variant associations in complex diseases Jennifer Asimit* and Eleftheria Zeggini by Asimit and Zeggini [5]), but many of them experience Abstract a large drop in power when both protective and risk The study of rare variants holds the promise of variants are present in a genetic region of interest. accounting for some of the missing heritability Indeed, over 20 different methods have been proposed in in complex traits. Next-generation sequencing the last 2 to 3 years, each with distinct properties under technologies enable probing of variation across the different allelic architecture scenarios [5]. full spectrum of allele frequencies. Multiple methods In a recent PLoS Genetics publication, Ionita-Laza et al. for the analysis of rare variants have been proposed [6] introduced a testing approach, referred to as a and, recently, Ionita-Laza et al. have presented an replication-based strategy that is less sensitive to the approach with the theoretical capacity to detect presence of both risk and protective variants in the risk and protective variants. The identication of region. Here, we discuss the method and the authors’ rare risk variants could have major implications in find ings when comparing it with two existing rare variant understanding complex disease etiopathogenesis. analysis methods proposed by Li and Leal [3] and by