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

Christoph Lange, Department of Biostatistics, Harvard School of Public Health, 655 Huntington Avenue, Boston, MA 02115, USA
Kristel van Steen, Department of Biostatistics, Harvard School of Public Health, 655 Huntington Ave, Boston, MA 02115
Toby Andrew, Twin Research & Genetic Epidemiology Unit, St Thomas' Hospital, London SE1 7EH, UK
Helen Lyon, Brigham and Women's Hospital, Harvard Medical School, Channing Laboratory, 181 Longwood Avenue, Boston, MA 02115, USA
Dawn L. DeMeo, Brigham and Women
Benjamin Raby, Brigham and Women's Hospital, Harvard Medical School, Channing Laboratory, 181 Longwood Avenue, Boston, MA 02115, USA
Amy Murphy, Department of Biostatistics, Harvard School of Public Health, 655 Huntington Avenue, Boston, MA 02115, USA
Edwin K. Silverman, Brigham and Women
Alex MacGregor , Twin Research & Genetic Epidemiology Unit, St Thomas' Hospital, London SE1 7EH, UK
Scott T. Weiss, Brigham and Women's Hospital, Harvard Medical School, Channing Laboratory, 181 Longwood Avenue, Boston, MA 02115, USA
Nan M. Laird, Department of Biostatistics, Harvard School of Public Health, 655 Huntington Avenue, Boston, MA 02115, USA

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.

Submitted: May 19, 2004 · Accepted: July 29, 2004 · Published: August 12, 2004

Recommended 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.; and 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: Vol. 3 : Iss. 1, Article 17.
DOI: 10.2202/1544-6115.1067
Available at: http://www.bepress.com/sagmb/vol3/iss1/art17

 
 
 
 

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