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Impact of Population Stratification on Family-Based Association Tests with Longitudinal Measurements

Author

Listed:
  • Ding Xiao

    (Harvard School of Public Health)

  • Weiss Scott

    (Harvard Medical School)

  • Raby Benjamin

    (Harvard Medical School)

  • Lange Christoph

    (Harvard School of Public Health)

  • Laird Nan M

    (Harvard School of Public Health)

Abstract

Several family-based approaches for testing genetic association with traits obtained from longitudinal or repeated measurement studies have been previously proposed. These approaches utilize the multivariate data more efficiently by using estimated optimal weights to combine univariate tests. We show that these FBAT approaches are still robust against hidden population stratification, but their power can be heavily affected since the estimated weights might provide poor approximation of the true theoretical optimal weights with the presence of population stratification. We introduce a permutation-based approach FBAT-MinP and an equal combination approach FBAT-EW, both of which do not involve the use of estimated weights. Through simulation studies, FBAT-MinP and FBAT-EW are shown to be powerful even in the presence of population stratification, when other approaches may substantially lose their power. An application of these approaches to the Childhood Asthma Management Program (CAMP) study data for testing an association between body mass index and a previously reported candidate SNP is given as an example.

Suggested Citation

  • Ding Xiao & Weiss Scott & Raby Benjamin & Lange Christoph & Laird Nan M, 2009. "Impact of Population Stratification on Family-Based Association Tests with Longitudinal Measurements," Statistical Applications in Genetics and Molecular Biology, De Gruyter, vol. 8(1), pages 1-17, February.
    • Handle: RePEc:bpj:sagmbi:v:8:y:2009:i:1:n:17
    DOI: 10.2202/1544-6115.1398
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    References listed on IDEAS

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    1. Neil J. Risch, 2000. "Searching for genetic determinants in the new millennium," Nature, Nature, vol. 405(6788), pages 847-856, June.
    2. Lange Christoph & van Steen Kristel & Andrew Toby & Lyon Helen & DeMeo Dawn L & Raby Benjamin & Murphy Amy & Silverman Edwin K & MacGregor Alex & Weiss Scott T & Laird Nan M, 2004. "A Family-Based Association Test for Repeatedly Measured Quantitative Traits Adjusting for Unknown Environmental and/or Polygenic Effects," Statistical Applications in Genetics and Molecular Biology, De Gruyter, vol. 3(1), pages 1-29, August.
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