Use of principal components to aggregate rare variants in case-control and family-based association studies in the presence of multiple covariates

BMC Proceedings

Proceedings

Thomas J Hoffmann¹  John S Witte¹  Rémi Kazma¹ 

[1] Department of Epidemiology and Biostatistics and Institute for Human Genetics, University of California San Francisco, Box 3110, 1450 Third Street, 94148-3110, San Francisco, CA, USA;

关键词: Minor Allele Frequency;    Common Variant;    Rare Variant;    Nonsynonymous Variant;    Genetic Score;   

DOI  :  10.1186/1753-6561-5-S9-S29

来源: Springer

【 摘 要 】

Rare variants may help to explain some of the missing heritability of complex diseases. Technological advances in next-generation sequencing give us the opportunity to test this hypothesis. We propose two new methods (one for case-control studies and one for family-based studies) that combine aggregated rare variants and common variants located within a region through principal components analysis and allow for covariate adjustment. We analyzed 200 replicates consisting of 209 case subjects and 488 control subjects and compared the results to weight-based and step-up aggregation methods. The principal components and collapsing method showed an association between the gene FLT1 and the quantitative trait Q1 (P<10−30) in a fraction of the computation time of the other methods. The proposed family-based test has inconclusive results. The two methods provide a fast way to analyze simultaneously rare and common variants at the gene level while adjusting for covariates. However, further evaluation of the statistical efficiency of this approach is warranted.

【 授权许可】

Unknown   
© Kazma et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.