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Segregation analysis of attention deficit hyperactivity disorder.

B S Maher¹, M L Marazita, H B Moss

¹Cleft Palate-Craniofacial Center, School of Dental Medicine, University of Pittsburgh, Pennsylvania 15261, USA.

American Journal of Medical Genetics

|March 2, 1999

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Genetic factors significantly influence attention deficit hyperactivity disorder (ADHD) symptom severity. This study suggests ADHD is an extreme manifestation of a heritable, continuous trait, with sex-dependent transmission patterns observed in affected families.

Area of Science:

Genetics
Psychiatry
Behavioral Science

Background:

Attention Deficit Hyperactivity Disorder (ADHD) is a complex neurodevelopmental disorder with suspected genetic underpinnings.
Understanding the mode of inheritance and genetic influences is crucial for developing targeted interventions.
Previous research indicates a significant heritable component, but the specific transmission patterns require further elucidation.

Purpose of the Study:

To investigate the role of genetic and environmental factors in the variability of Attention Deficit Hyperactivity Disorder (ADHD) symptom counts.
To determine the mode of inheritance for ADHD, treating symptom count as a quantitative trait.
To examine sex-dependent effects and covariate influences (socioeconomic status) on ADHD symptom transmission.

Main Methods:

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Segregation analysis was performed on 495 nuclear families ascertained for paternal substance abuse.
ADHD symptom count (DSM-III-R) was analyzed as a quantitative trait using class A and D regressive models.
Analyses were conducted on the full dataset and a subgroup of 130 families with at least one diagnosed member, assessing sex dependence and covariates.

Main Results:

Analysis of the full dataset suggested a transmissible, non-Mendelian major effect influencing ADHD symptom count.
In a subgroup of families with diagnosed ADHD, a sex-dependent Mendelian codominant model provided the best fit, rejecting other models.
Covariate effects did not significantly improve model fit in the subgroup, indicating strong genetic influence.

Conclusions:

The findings support Mendelian transmission of ADHD symptom count in a clinically relevant population.
ADHD appears to be an extreme manifestation of an underlying heritable, continuous trait.
Sex-dependent genetic factors play a significant role in the transmission of ADHD symptoms.