A family based association test for repeatedly measured quantitative traits adjusting for unknown environmental and/or polygenic effects

Christoph Lange; Kristel van Steen; Toby Andrew; Helen Lyon; Dawn L. DeMeo; Benjamin Raby; Amy Murphy; Edwin K. Silverman; Alex MacGregor; Scott T. Weiss; Nan M. Laird

doi:10.2202/1544-6115.1067

A family based association test for repeatedly measured quantitative traits adjusting for unknown environmental and/or polygenic effects

Christoph Lange, Kristel van Steen, Toby Andrew, Helen Lyon, Dawn L. DeMeo, Benjamin Raby, Amy Murphy, Edwin K. Silverman, Alex MacGregor, Scott T. Weiss, Nan M. Laird

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78 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1-17
Number of pages	17
Journal	Statistical Applications in Genetics and Molecular Biology
Volume	3
Issue number	1
DOIs	https://doi.org/10.2202/1544-6115.1067
Publication status	Published - 2004

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10.2202/1544-6115.1067

Cite this

Lange, C., van Steen, K., Andrew, T., Lyon, H., DeMeo, D. L., Raby, B., Murphy, A., Silverman, E. K., MacGregor, A., Weiss, S. T., & Laird, N. 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, 3(1), 1-17. https://doi.org/10.2202/1544-6115.1067

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title = "A family based association test for repeatedly measured quantitative traits adjusting for unknown environmental and/or polygenic effects",

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.",

author = "Christoph Lange and {van Steen}, Kristel and Toby Andrew and Helen Lyon and DeMeo, {Dawn L.} and Benjamin Raby and Amy Murphy and Silverman, {Edwin K.} and Alex MacGregor and Weiss, {Scott T.} and Laird, {Nan M.}",

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language = "English",

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Lange, C, van Steen, K, Andrew, T, Lyon, H, DeMeo, DL, Raby, B, Murphy, A, Silverman, EK, MacGregor, A, Weiss, ST & Laird, NM 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, no. 1, pp. 1-17. https://doi.org/10.2202/1544-6115.1067

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T1 - A family based association test for repeatedly measured quantitative traits adjusting for unknown environmental and/or polygenic effects

AU - Lange, Christoph

AU - van Steen, Kristel

AU - Andrew, Toby

AU - Lyon, Helen

AU - DeMeo, Dawn L.

AU - Raby, Benjamin

AU - Murphy, Amy

AU - Silverman, Edwin K.

AU - MacGregor, Alex

AU - Weiss, Scott T.

AU - Laird, Nan M.

PY - 2004

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AB - 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.

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