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Original Investigation |

Population-Based, Multigenerational Family Clustering Study of Obsessive-compulsive Disorder

David Mataix-Cols, PhD1,2; Marcus Boman, BSc3; Benedetta Monzani, MSc1; Christian Rück, MD4; Eva Serlachius, MD4; Niklas Långström, MD3; Paul Lichtenstein, PhD3
[+] Author Affiliations
1Department of Psychosis Studies, Institute of Psychiatry, King’s College London, London, England
2Department of Psychology, Institute of Psychiatry, King’s College London, London, England
3Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
4Division of Psychiatry, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
JAMA Psychiatry. 2013;70(7):709-717. doi:10.1001/jamapsychiatry.2013.3.
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Importance  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.

Objective  To provide unbiased estimates of familial risk for and heritability of OCD at the population level.

Design and Setting  Population-based, multigenerational, case-control family and twin studies using the Swedish National Patient Register, Multi-Generation Register, and Twin Register.

Participants  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.

Results  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 heritability estimates.

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.

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Figures

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Figure 1.
Risk For Obsessive-Compulsive Disorder Among Relatives With Differing Genetic and Environmental Distance to All Diagnosed Obsessive-Compulsive Disorder Cases in the Swedish National Patient Register (1969-2009) Compared With Matched Population Control Subjects

Each individual in the study population may appear multiple times in different categories (eg, parent, sibling, and cousin) depending on family pedigree. Red indicates first-degree relatives; green, second-degree relatives; yellow, third-degree relatives; and blue, nonbiological relatives. Nonbiological relatives are individuals who have at least 1 child together with the proband with obsessive-compulsive disorder.

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Figure 2.
Polychoric Correlations for Self-reported Obsessive-Compulsive Symptoms

Polychoric correlations for self-reported obsessive-compulsive symptoms among 16 383 twins aged 20 to 47 years in the Screening Twin Adults: Genes and Environment (STAGE) study, stratified by zygosity and sex. DZF indicates dizygotic female; DZM, dizygotic male; DZOS, dizygotic opposite-sex; MZF, monozygotic female; and MZM, monozygotic male. Red indicates male twin pairs; green, female twin pairs; and yellow, opposite-sex twins.

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