Complex segregation analysis provides compelling evidence for a major gene underlying obsessive-compulsive disorder and for heterogeneity by sex.
Evidence from twin and family studies supports a genetic etiology for obsessive-compulsive disorder (OCD). The purpose of this study was to test whether a major gene is implicated in a proportion of families with OCD. Complex segregation analyses of 153 families (80 case and 73 control), ascertained in the Johns Hopkins OCD Family Study, provided strong evidence for a major gene. A Mendelian-dominant model, with significant sex effects and with residual familial effects, best explained the observed data. Stratification of the sample by the sex of probands provided further evidence of heterogeneity with respect to familial aggregation. Segregation analyses of 86 families with a female proband and of the 67 families with a male proband suggested that a Mendelian-dominant model with familial residual effects was the most parsimonious model explaining the inheritance of OCD in both subgroups.
Nestadt
G
G
Department of Psychiatry and Behavioral Sciences, School of Medicine, The Johns Hopkins University, Baltimore, MD 21287, USA. gnestadt@mail.jhmi.edu
Lan
T
T
Samuels
J
J
Riddle
M
M
Bienvenu
O J
OJ
Liang
K Y
KY
Hoehn-Saric
R
R
Cullen
B
B
Grados
M
M
Beaty
T H
TH
Shugart
Y Y
YY
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D016022:Case-Control Studies; D002648:Child; D020090:Chromosome Segregation / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D018740:Genetic Heterogeneity; D008040:Genetic Linkage / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D020412:Multifactorial Inheritance / Q000235:genetics; D009771:Obsessive-Compulsive Disorder / Q000453:epidemiology / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012727:Sex Characteristics