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Confounding from cryptic relatedness in haplotype-based association studies

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Abstract

Cryptic relatedness was suggested to be an important source of confounding in population-based association studies (PBAS). The impact of cryptic relatedness on the performance of haplotype phase inference and haplotype-based association tests is not clear. In this study, we used the Hapmap genetic data to simulate a set of related samples. We evaluated the accuracy of haplotype phase inferred by PHASE 2.1 and calculated the power, type I error rates, accuracy and positive prediction value (PPV) of haplotype frequency-based association tests (HFAT) and haplotype similarity-based association tests (HSAT) under various scenarios, considering relatedness levels, disease models and sample sizes. Cryptic relatedness appeared to slightly increase the accuracy of haplotype phase inference. We observed significant negative effect of cryptic relatedness on the performance of HFAT and HSAT. Ignoring cryptic relatedness may increase spurious association results in haplotype-based PBAS.

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Acknowledgments

Investigators of this work were partially supported by grants from NIH (R01 AR050496, R21 AG027110, R01 AG026564, P50 AR055081 and R21 AA015973). The study was also benefited from grants from National Science Foundation of China, Huo Ying Dong Education Foundation, HuNan Province, Xi’an Jiaotong University, and the Ministry of Education of China.

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Authors and Affiliations

  1. College of Medicine, Xi’an Jiaotong University, 710061, Xi’an, People’s Republic of China

    Feng Zhang

  2. College of Life Sciences and Engineering, Beijing Jiaotong University, 100044, Beijing, People’s Republic of China

    Hong-Wen Deng

  3. Departments of Orthopedic Surgery and Basic Medical Science, School of Medicine, University of Missouri-Kansas City, 2411 Holmes Street, Room: M3-C03, Kansas City, MO, 64108, USA

    Hong-Wen Deng

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  1. Feng Zhang
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  2. Hong-Wen Deng
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Correspondence to Feng Zhang or Hong-Wen Deng.

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Zhang, F., Deng, HW. Confounding from cryptic relatedness in haplotype-based association studies. Genetica 138, 945–950 (2010). https://doi.org/10.1007/s10709-010-9476-6

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  • DOI: https://doi.org/10.1007/s10709-010-9476-6

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