Statistics and Its Interface

Volume 2 (2009)

Number 2

Detecting essential and removable interactions in genome-wide association studies

Pages: 161 – 170

DOI: http://dx.doi.org/10.4310/SII.2009.v2.n2.a6

Authors

Andrew Dewan (Yale School of Public Health, Yale University, New Haven, Conn., U.S.A.)

Robert Dubrow (Yale School of Public Health, Yale University, New Haven, Conn., U.S.A.)

Josephine Hoh (Yale School of Public Health, Yale University, New Haven, Conn., U.S.A.)

Xiangtao Liu (Department of Applied Mathematics, Yale University, New Haven, Conn., U.S.A.)

Chengqing Wu (Yale School of Public Health, Yale University, New Haven, Conn., U.S.A.)

Yaning Yang (Department of Statistics and Finance, University of Science and Technology of China, Hefei, Anhui, China)

Zhiliang Ying (Department of Statistics, Columbia University, New York, N.Y., U.S.A.)

Hong Zhang (Department of Statistics and Finance, University of Science and Technology of China, Hefei, Anhui, China)

Abstract

Detection of disease gene interaction effects among the enormous array of single nucleotide polymorphism (SNP) combinations represents the next frontier in genome-wide association (GWA) studies. Here we propose a novel strategy on the basis of the pattern and nature of the interaction, which can be classified as essential (EI) or removable (RI). We provide an analytical framework, including the qualitative conditions for screening EIs/RIs and a RI-to-EI likelihood ratio score to quantitatively measure the effect. In analyzing six GWA data sets, we find that the scores follow an exponential distribution, except in the upper $10^{-8}$ tail region in which the scores become irregular and unpredictable. Our approach is conceptually simple, computationally efficient and detects interactions that can be visualized and unequivocally interpreted.

Keywords

genome-wide association study, gene-gene interaction, removable interaction, essential interaction, likelihood ratio statistics

2010 Mathematics Subject Classification

Primary 62F03, 62P10. Secondary 92D10.

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