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Inference of the Haplotype Effect in a Matched Case-Control Study Using Unphased Genotype Data

Author

Listed:
  • Sinha Samiran

    (Texas A&M University)

  • Gruber Stephen B

    (University of Michigan)

  • Mukherjee Bhramar

    (University of Michigan)

  • Rennert Gad

    (Carmel Medical Center; Technion-Israel Institute of Technology; CHS National Cancer Control Center)

Abstract

Typically locus specific genotype data do not contain information regarding the gametic phase of haplotypes, especially when an individual is heterozygous at more than one locus among a large number of linked polymorphic loci. Thus, studying disease-haplotype association using unphased genotype data is essentially a problem of handling a missing covariate in a case-control design. There are several methods for estimating a disease-haplotype association parameter in a matched case-control study. Here we propose a conditional likelihood approach for inference regarding the disease-haplotype association using unphased genotype data arising from a matched case-control study design. The proposed method relies on a logistic disease risk model and a Hardy-Weinberg equilibrium (HWE) among the control population only. We develop an expectation and conditional maximization (ECM) algorithm for jointly estimating the haplotype frequency and the disease-haplotype association parameter(s). We apply the proposed method to analyze the data from the Alpha-Tocopherol, Beta-Carotene Cancer prevention study, and a matched case-control study of breast cancer patients conducted in Israel. The performance of the proposed method is evaluated via simulation studies.

Suggested Citation

  • Sinha Samiran & Gruber Stephen B & Mukherjee Bhramar & Rennert Gad, 2008. "Inference of the Haplotype Effect in a Matched Case-Control Study Using Unphased Genotype Data," The International Journal of Biostatistics, De Gruyter, vol. 4(1), pages 1-26, May.
    • Handle: RePEc:bpj:ijbist:v:4:y:2008:i:1:n:6
    DOI: 10.2202/1557-4679.1079
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    References listed on IDEAS

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    1. H. Zhang & G. Zheng & Z. Li, 2006. "Statistical Analysis for Haplotype-Based Matched Case–Control Studies," Biometrics, The International Biometric Society, vol. 62(4), pages 1124-1131, December.
    2. Lin, D.Y. & Zeng, D., 2006. "Likelihood-Based Inference on Haplotype Effects in Genetic Association Studies," Journal of the American Statistical Association, American Statistical Association, vol. 101, pages 89-104, March.
    3. Glen A. Satten & Raymond J. Carroll, 2000. "Conditional and Unconditional Categorical Regression Models with Missing Covariates," Biometrics, The International Biometric Society, vol. 56(2), pages 384-388, June.
    4. Jinbo Chen & Nilanjan Chatterjee, 2006. "Haplotype-Based Association Analysis in Cohort and Nested Case–Control Studies," Biometrics, The International Biometric Society, vol. 62(1), pages 28-35, March.
    Full references (including those not matched with items on IDEAS)

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