Comparative study of statistical methods for detecting association with rare variants in exome-resequencing data

BMC Proceedings

Proceedings

Matthias Macé¹  Mohamad Saad²  Aude Saint Pierre²  Nora Bohossian²  Maria Martinez² 

[1] INSERM UMR1043, CPTP, CHU Purpan, 31024, Toulouse, France;INSERM UMR1043, CPTP, CHU Purpan, 31024, Toulouse, France;Université Paul Sabatier, Toulouse, France;

关键词: Minor Allele Frequency;    Rare Variant;    Causal Gene;    Unrelated Individual;    Causal Variant;   

DOI  :  10.1186/1753-6561-5-S9-S33

来源: Springer

【 摘 要 】

Genome-wide association studies for complex traits are based on the common disease/common variant (CDCV) and common disease/rare variant (CDRV) assumptions. Under the CDCV hypothesis, classical genome-wide association studies using single-marker tests are powerful in detecting common susceptibility variants, but under the CDRV hypothesis they are not as powerful. Several methods have been recently proposed to detect association with multiple rare variants collectively in a functional unit such as a gene. In this paper, we compare the relative performance of several of these methods on the Genetic Analysis Workshop 17 data. We evaluate these methods using the unrelated individual and family data sets. Association was tested using 200 replicates for the quantitative trait Q1. Although in these data the power to detect association is often low, our results show that collapsing methods are promising tools. However, we faced the challenge of assessing the proper type I error to validate our power comparisons. We observed that the type I error rate was not well controlled; however, we did not find a general trend specific to each method. Each method can be conservative or nonconservative depending on the studied gene. Our results also suggest that collapsing and the single-locus association approaches may not be affected to the same extent by population stratification. This deserves further investigation.

【 授权许可】

CC BY   
© Saad et al; licensee BioMed Central Ltd. 2011