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A variance component based multi-marker association test using family and unrelated data

Xuefeng Wang1, Nathan J Morris2, Xiaofeng Zhu2* and Robert C Elston2

Author Affiliations

1 Department of Biostatistics, Harvard School of Public Health, Boston, MA, 02115, USA

2 Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, 44106, USA

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BMC Genetics 2013, 14:17  doi:10.1186/1471-2156-14-17

Published: 4 March 2013

Abstract

Background

Incorporating family data in genetic association studies has become increasingly appreciated, especially for its potential value in testing rare variants. We introduce here a variance-component based association test that can test multiple common or rare variants jointly using both family and unrelated samples.

Results

The proposed approach implemented in our R package aggregates or collapses the information across a region based on genetic similarity instead of genotype scores, which avoids the power loss when the effects are in different directions or have different association strengths. The method is also able to effectively leverage the LD information in a region and it can produce a test statistic with an adaptively estimated number of degrees of freedom. Our method can readily allow for the adjustment of non-genetic contributions to the familial similarity, as well as multiple covariates.

Conclusions

We demonstrate through simulations that the proposed method achieves good performance in terms of Type I error control and statistical power. The method is implemented in the R package “fassoc”, which provides a useful tool for data analysis and exploration.

Keywords:
Association studies; Family data; Score test; Multi-marker test