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Fitting ACE structural equation models to case-control family data
K N Javaras1, J I Hudson, N M Laird
1Waisman Laboratory for Brain Imaging & Behavior, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA. javaras@wisc.edu
Genetic Epidemiology
|November 18, 2009
Summary
This study introduces a new statistical method to analyze family disease data, accurately estimating genetic and environmental factors contributing to diseases like depression. The approach provides reliable heritability estimates from case-control family studies.
Area of Science:
- Behavioral Genetics
- Biostatistics
- Psychiatric Epidemiology
Background:
- Family studies are crucial for understanding disease aggregation.
- Case-control family data are often collected but underutilized for genetic and environmental analyses.
- Classic twin models (ACE) estimate additive genetic (A), shared environment (C), and unique environment (E) effects.
Purpose of the Study:
- To develop a likelihood-based method for fitting ACE models to case-control family data.
- To enable valid estimation of genetic and environmental variance components from case-control data.
- To extend the application of ACE models beyond population-based family studies.
Main Methods:
- Description of a structural equation ACE model for binary family data.
- Development of a likelihood-based fitting approach for singly ascertained case-control family data.
- Conditioning on proband disease status and setting prevalence to estimate variance components.
Main Results:
- Simulation studies indicate approximately unbiased estimates of A, C, and E variance components.
- The method successfully estimates genetic and environmental contributions to disease risk.
- Application to Austrian depression data yielded heritability estimates comparable to twin studies.
Conclusions:
- The proposed likelihood-based approach enables robust estimation of genetic and environmental influences on disease from case-control family data.
- This method expands the utility of case-control family studies for etiological research.
- Accurate estimation of heritability and environmental factors is now possible using case-control family designs.
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