Segregation analysis of obsessive-compulsive disorder using symptom-based factor scores.
Obsessive-compulsive disorder (OCD) is a complex psychiatric disorder characterized by recurring obsessions or compulsions that cause significant distress to the patient or significantly interfere with the patient's normal home, work, or social activities [Diagnostic and Statistical Manual of Mental Disorders, 4th Edition. Washington, DC: American Psychiatric Association, 1994]. Twin and family studies have suggested that OCD has a significant genetic component. We performed complex segregation analyses using POINTER with families ascertained through an OCD-affected proband. In an attempt to resolve the phenotypic heterogeneity observed among individuals with OCD these segregation analyses used four factor-analytic symptom dimensions to subset the family sample based upon probands' symptom factor scores. Analysis of the entire sample allowed rejection of only the no transmission model; that model was also rejected in all subsequent analyses. Limiting the analyses to families with at least one OCD-affected member in addition to the proband (the demonstrably familial form of OCD) allowed rejection of all models except the mixed model. Analyses limited to families of high-factor-3 (symmetry and ordering symptoms) probands led to rejection of the polygenic model, indicating the involvement of a major locus. Additionally, the relative risk of OCD or subclinical OCD was 1.7 for relatives of probands with a factor 3 score greater than zero compared with relatives of probands with a low factor score. The symptoms attributed to high factor 3 scores (symmetry and ordering) may constitute a genetically significant symptomatic subtype of OCD. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:669-675, 1999.
Alsobrook II
J P
JP
Child Study Center, Yale University School of Medicine, New Haven, Connecticut, USA. john.alsobrook@yale.edu
Leckman
J F
JF
Goodman
W K
WK
Rasmussen
S A
SA
Pauls
D L
DL
D000375:Aging; D001526:Behavioral Symptoms; D020090:Chromosome Segregation; D003193:Compulsive Personality Disorder / Q000235:genetics* / Q000523:psychology*; D005192:Family Health; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D005808:Genes, Recessive / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D016013:Likelihood Functions; D008297:Male; D008957:Models, Genetic; D020412:Multifactorial Inheritance / Q000235:genetics; D011581:Psychological Tests