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Segregation analysis of obsessive-compulsive disorder using symptom-based factor scores
J P Alsobrook II1, J F Leckman, W K Goodman
1Child Study Center, Yale University School of Medicine, New Haven, Connecticut, USA. john.alsobrook@yale.edu
American Journal of Medical Genetics
|December 3, 1999
Summary
Genetic studies suggest obsessive-compulsive disorder (OCD) has a hereditary basis. Research indicates symmetry and ordering symptoms may represent a distinct genetic subtype of OCD, influencing familial risk.
Area of Science:
- Psychiatric Genetics
- Behavioral Genetics
- Clinical Psychology
Background:
- Obsessive-compulsive disorder (OCD) is a complex psychiatric condition with significant patient distress and functional impairment.
- Previous twin and family studies indicate a substantial genetic contribution to OCD etiology.
- Phenotypic heterogeneity in OCD complicates genetic analyses, necessitating subgroup investigations.
Purpose of the Study:
- To investigate the genetic transmission patterns of obsessive-compulsive disorder (OCD) using complex segregation analysis.
- To explore whether specific symptom dimensions of OCD represent genetically distinct subtypes.
- To determine the role of a major gene locus in OCD, particularly within symptom-defined subgroups.
Main Methods:
- Complex segregation analyses were performed using the POINTER software on families ascertained through an OCD-affected proband.
- The family sample was subsetted based on four factor-analytic symptom dimensions derived from probands' symptom factor scores to address phenotypic heterogeneity.
- Analyses were conducted on the entire sample, the demonstrably familial form of OCD (families with >1 affected member), and families with high factor-3 (symmetry/ordering) symptom scores.
Main Results:
- Segregation analyses rejected the null model of no transmission for the entire sample and subsequent analyses.
- For the demonstrably familial form of OCD, all models except the mixed model were rejected.
- Analyses of families with high factor-3 scores rejected the polygenic model, suggesting a major locus involvement.
- Relatives of probands with high factor-3 scores (symmetry/ordering) had a 1.7 times higher relative risk of OCD or subclinical OCD compared to relatives of probands with low factor scores.
Conclusions:
- The findings support a significant genetic component in OCD, with evidence against a purely polygenic model in certain subgroups.
- Symptom dimensions related to symmetry and ordering (factor 3) may represent a genetically significant subtype of OCD.
- Identifying genetically distinct subtypes could improve understanding and treatment of OCD.