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Family factors and sampling approach differentially influence attention deficit/hyperactivity disorder subtypes
R D Todd1, C A Joyner, T H-C Ji
1Washington University School of Medicine, Departments of Psychiatry & Genetics, St Louis, MO 63110, USA. toddr@psychiatry.wustl.edu
Molecular Psychiatry
|April 20, 2004
Summary
The transmission disequilibrium test (TDT) may miss ADHD susceptibility genes when only two-parent families participate. This study found combined subtype ADHD with conduct disorder was less common in trios, impacting genetic association studies.
Area of Science:
- Genetics
- Psychiatry
- Biostatistics
Background:
- The transmission disequilibrium test (TDT) is a common genetic association analysis method.
- Previous research suggested that excluding families with only one parent (duos) might reduce the power of TDT for certain Attention-Deficit/Hyperactivity Disorder (ADHD) subtypes.
- This could be due to ascertainment bias, where specific ADHD presentations are less likely to be observed in complete trios.
Purpose of the Study:
- To investigate whether the exclusion of parent-proband duos affects the detection of ADHD subtypes in genetic association studies.
- To test the hypothesis that certain ADHD subtypes, specifically combined subtype ADHD with conduct disorder, are underrepresented in trio families.
- To control for other family and proband characteristics in a multivariable logistic regression model.
Main Methods:
- Utilized a population-based sample of twin families.
- Employed multivariable logistic regression to analyze genetic association data.
- Defined ADHD subtypes using both latent class analysis and Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria.
- Controlled for proband sex, age, and comorbid conduct or oppositional defiant disorder.
Main Results:
- Proband sex, comorbid conduct disorder, or oppositional defiant disorder significantly predicted ADHD diagnosis across both latent class and DSM-IV definitions.
- Younger age was also a significant predictor for the combined subtype of ADHD.
- Combined subtype ADHD with comorbid conduct disorder was significantly less frequent in families with two participating parents (trios).
- Conduct disorder without ADHD did not show a difference in frequency based on the number of participating parents.
Conclusions:
- The findings support the hypothesis that certain ADHD presentations, particularly combined subtype ADHD with conduct disorder, are less common in trio families.
- This underrepresentation in trios could indeed reduce the power of the TDT and similar genetic association tests to detect susceptibility genes for these specific ADHD subtypes.
- Researchers should consider the potential impact of family structure on genetic association study results for ADHD.
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