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Updated: May 26, 2026

A Pathway Association Study Tool for GWAS Analyses of Metabolic Pathway Information
Published on: July 1, 2020
Some capabilities for model-based and model-free linkage analysis using the program package S.A.G.E. (Statistical
1Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH 44106, USA.
The Statistical Analysis for Genetic Epidemiology (SAGE) package enhances genetic linkage analysis for complex traits. It improves power for quantitative and binary traits, especially when incorporating age of onset information.
Area of Science:
- Genetics
- Epidemiology
- Biostatistics
Background:
- Genetic linkage analysis is crucial for identifying genes influencing complex diseases.
- Accurate modeling of trait inheritance is essential for robust linkage detection.
- The Statistical Analysis for Genetic Epidemiology (SAGE) software offers advanced capabilities for genetic analysis.
Purpose of the Study:
- To demonstrate the utility of the SAGE program package for model-based linkage analysis.
- To highlight SAGE's capabilities in analyzing both continuous and binary traits with variable age of onset.
- To showcase improved statistical power by incorporating age of onset for complex traits.
Main Methods:
- Utilized model-based linkage analysis within the SAGE program package.
- Performed segregation analysis to establish the best-fitting genetic model for a quantitative trait (plasma dopamine β hydroxylase).
- Transformed a binary trait (schizophrenia) with variable age of onset into a quantitative susceptibility trait to enhance linkage signals.
Main Results:
- Successfully applied SAGE for model-based linkage analysis of a quantitative trait under monogenic inheritance.
- Demonstrated that using age of onset information for a binary trait (schizophrenia) significantly increased the statistical power of linkage signals.
- The SAGE package proved effective in handling traits with complex inheritance patterns and variable age of onset.
Conclusions:
- The SAGE program package provides powerful tools for genetic linkage analysis, particularly for traits with complex inheritance.
- Incorporating age of onset information can substantially improve the power to detect genetic linkage for binary traits.
- SAGE facilitates sophisticated genetic epidemiological studies by enabling detailed trait modeling and analysis.
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