Does pathway analysis make it easier for common variants to tag rare ones?

BMC Proceedings

Proceedings

Jeanine J Houwing-Duistermaat¹  Roula Tsonaka¹  Hae-Won Uh² 

[1] Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Einthovenweg 20, 2333 ZC, Leiden, The Netherlands;Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Einthovenweg 20, 2333 ZC, Leiden, The Netherlands;Netherlands Consortium for Healthy Ageing, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands;

关键词: Common Variant;    Rare Variant;    Ridge Regression;    Global Test;    Common SNPs;   

DOI  :  10.1186/1753-6561-5-S9-S90

来源: Springer

【 摘 要 】

Analyzing sequencing data is difficult because of the low frequency of rare variants, which may result in low power to detect associations. We consider pathway analysis to detect multiple common and rare variants jointly and to investigate whether analysis at the pathway level provides an alternative strategy for identifying susceptibility genes. Available pathway analysis methods for data from genome-wide association studies might not be efficient because these methods are designed to detect common variants. Here, we investigate the performance of several existing pathway analysis methods for sequencing data. In particular, we consider the global test, which does not consider linkage disequilibrium between the variants in a gene. We improve the performance of the global test by assigning larger weights to rare variants, as proposed in the weighted-sum approach. Our conclusion is that straightforward application of pathway analysis is not satisfactory; hence, when common and rare variants are jointly analyzed, larger weights should be assigned to rare variants.

【 授权许可】

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