Back to Browse Journals » Advances and Applications in Bioinformatics and Chemistry » Volume 5

A rapid method for combined analysis of common and rare variants at the level of a region, gene, or pathway

Authors Curtis D

Received 17 April 2012

Accepted for publication 7 May 2012

Published 24 July 2012 Volume 2012:5 Pages 1—9

DOI https://doi.org/10.2147/AABC.S33049

Review by Single-blind

Peer reviewer comments 2

David Curtis

Centre for Psychiatry, Barts and the London School of Medicine and Dentistry, London, UK

Abstract: Previously described methods for the combined analysis of common and rare variants have disadvantages such as requiring an arbitrary classification of variants or permutation testing to assess statistical significance. Here we propose a novel method which implements a weighting scheme based on allele frequencies observed in both cases and controls. Because the test is unbiased, scores can be analyzed with a standard t-test. To test its validity we applied it to data for common, rare, and very rare variants simulated under the null hypothesis. To test its power we applied it to simulated data in which association was present, including data using the observed allele frequencies of common and rare variants in NOD2 previously reported in cases of Crohn’s disease and controls. The method produced results that conformed well to those expected under the null hypothesis. It demonstrated more power to detect association when rare and common variants were analyzed jointly, the power further increasing when rare variants were assigned higher weights. 20,000 analyses of a gene containing 62 variants could be performed in 80 minutes on a laptop. This approach shows promise for the analysis of data currently emerging from genome wide sequencing studies.

Keywords: common, rare, variant, sequence, genome, exome

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]

 

Readers of this article also read:

The hemagglutinin of the influenza A(H1N1)pdm09 is mutating towards stability

Castelán-Vega JA, Magaña-Hernández A, Jiménez-Alberto A, Ribas-Aparicio RM

Advances and Applications in Bioinformatics and Chemistry 2014, 7:37-44

Published Date: 3 October 2014

Genetic and chemical knockdown: a complementary strategy for evaluating an anti-infective target

Ramachandran V, Singh R, Yang X, Tunduguru R, Mohapatra S, Khandelwal S, Patel S, Datta S

Advances and Applications in Bioinformatics and Chemistry 2013, 6:1-13

Published Date: 7 February 2013

FDR-FET: an optimizing gene set enrichment analysis method

Rui-Ru Ji, Karl-Heinz Ott, Roumyana Yordanova, et al

Advances and Applications in Bioinformatics and Chemistry 2011, 4:37-42

Published Date: 15 March 2011

LifePrint: a novel k-tuple distance method for construction of phylogenetic trees

Fabián Reyes-Prieto, Adda J García-Chéquer, Hueman Jaimes-Díaz, et al

Advances and Applications in Bioinformatics and Chemistry 2011, 4:13-27

Published Date: 20 January 2011