Controlled family studies have consistently found that obsessive-compulsive disorder (OCD)
aggregates in families but have typically relied on samples recruited from specialist clinics.
Furthermore, previous studies could not disentangle genetic from environmental factors contributing
to the observed familiality.
To provide unbiased estimates of familial risk for and heritability of OCD at the population
Design and Setting
Population-based, multigenerational, case-control family and twin studies using the Swedish
National Patient Register, Multi-Generation Register, and Twin Register.
All individuals diagnosed as having OCD between January 1, 1969, and December 31, 2009
(n = 24 768) and all their available first-, second-, and third-degree relatives,
as well as nonbiological relatives and matched general population control subjects. Twins
(n = 16 383) were included from the population-based Twin Register.
Main Outcome and Measure
The risk for OCD among relatives of OCD probands.
The risk for OCD among relatives of OCD probands increased proportionally to the degree of
genetic relatedness. The risk for first-degree relatives was significantly higher than that for
second- and third-degree and nonbiological relatives. Second-degree relatives had higher risk for
OCD than third-degree relatives. Relatives at similar genetic distances had similar risks for OCD,
despite different degrees of shared environment. Separate twin modeling analyses confirmed that
familial risk for OCD was largely attributable to additive genetic factors (47%; 95% CI, 42%-52%),
with no significant effect of shared environment. Nonbiological relatives (spouses or partners who
have at least 1 child together) also had an elevated risk for OCD (odds ratio, 2.61; 95% CI,
1.99-3.42). Early-onset probands (3907 individuals; mean age, 13.7 years) had slightly
(nonsignificantly) higher familial risk than the total sample, although this was substantially lower
than previously reported. There were no significant sex differences in the familial pattern or
Conclusions and Relevance
Obsessive-compulsive disorder clusters in families primarily due to genetic factors. Nonshared
environmental factors are at least as important. The quest for candidate genes, nonshared
environmental risk factors, and their possible correlation or interaction should continue. The
finding of possible assortative mating in OCD is intriguing and should be investigated further.