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A Family-Based Association Test for Repeatedly Measured Quantitative Traits Adjusting for Unknown Environmental and/or Polygenic Effects

Author

Listed:
  • Lange Christoph

    (Harvard School of Public Health)

  • van Steen Kristel

    (Harvard School of Public Health)

  • Andrew Toby

    (St Thomas’ Hospital, London SE1 7EH, UK)

  • Lyon Helen

    (Harvard Medical School)

  • DeMeo Dawn L

    (Brigham and Women)

  • Raby Benjamin

    (Harvard Medical School)

  • Murphy Amy

    (Harvard School of Public Health)

  • Silverman Edwin K

    (Brigham and Women)

  • MacGregor Alex

    (St Thomas’ Hospital, London)

  • Weiss Scott T

    (Harvard Medical School)

  • Laird Nan M

    (Harvard School of Public Health)

Abstract

We propose a family-based association test, FBAT-PC, for studies with quantitative traits that are measured repeatedly. The traits may be influenced by partially or completely unknown factors that may vary for each measurement. Using generalized principal component analysis, FBAT-PC amplifies the genetic effects of each measurement by constructing an overall phenotype with maximal heritability. Analytically, and in the simulation studies, we compare FBAT-PC with standard methodology and assess both the heritability of the overall phenotype and the power of FBAT-PC. Compared to univariate analysis, FBAT-PC achieves power gains of up to 200%. Applications of FBAT-PC to an osteoporosis study and to an asthma study show the practical relevance of FBAT-PC. FBAT-PC has been implemented in the software package PBAT and is freely available at http://www.biostat.harvard.edu/~clange/default.htm.

Suggested Citation

  • 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.
    • Handle: RePEc:bpj:sagmbi:v:3:y:2004:i:1:n:17
    DOI: 10.2202/1544-6115.1067
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    Cited by:

    1. 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.
    2. Zhenchuan Wang & Qiuying Sha & Shuanglin Zhang, 2016. "Joint Analysis of Multiple Traits Using "Optimal" Maximum Heritability Test," PLOS ONE, Public Library of Science, vol. 11(3), pages 1-12, March.
    3. Lei Zhang & Aaron J Bonham & Jian Li & Yu-Fang Pei & Jie Chen & Christopher J Papasian & Hong-Wen Deng, 2009. "Family-Based Bivariate Association Tests for Quantitative Traits," PLOS ONE, Public Library of Science, vol. 4(12), pages 1-9, December.

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