Abstract
The ‘large p, small n’ problem in genomewide association studies (GWAS) is an important subject in genetic studies. Many approaches have been proposed for this issue, but none of them successfully combine the Haseman–Elston (H–E) regression with sliding-window scan approaches in GWAS. In this article, we extended H–E regression to GWAS, and replaced original data with different measurements of phenotype of sib pairs. Meanwhile, we also applied hidden Markov model to infer identity by state. Using subsequent simulation studies, we found that it had higher statistical power than the corresponding single-marker association studies. The advantage of the H–E regression was also sufficient to capture about 48.01% of the quantitative trait locus (QTL). Meanwhile, the results show that the power decreases with the increase in the number of QTLs, and the power of H–E regression is sensitive to heritability.
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Acknowledgements
We thank the editor and referees for helpful comments. This work was supported by the National Natural Science Foundation of China (grant no. 31460594), China Scholarship Council (grant no. 201308155140), Hetao College teaching and research project (grant no. HTXYJZ14005).
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Corresponding editor: Rajiva Raman
Bujun Mei initiated the idea, developed the theory and derived the equations; and wrote the paper. Zhihua Wang conducted the simulation studies and obtained the analytical results. All authors approved the final version of the paper.
[Mei B. and Wang Z. 2016 An efficient method to handle the ‘large p, small n’ problem for genomewide association studies using Haseman–Elston regression. J. Genet. 95, xx–xx]
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MEI, B., WANG, Z. An efficient method to handle the ‘large p, small n’ problem for genomewide association studies using Haseman–Elston regression. J Genet 95, 847–852 (2016). https://doi.org/10.1007/s12041-016-0705-3
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DOI: https://doi.org/10.1007/s12041-016-0705-3