Obsessive-Compulsive Disorder Transmitted Through Genetic Relationship

The genetic relationship between parents and offspring is largely responsible for the transmission of obsessive-compulsive disorder (OCD) with rearing in a minor role. These study findings were published in the Journal of the American Medical Association Psychiatry.

The lifetime prevalence of OCD is estimated to be 1.3% and it aggregates in families as well.

Investigators sought to assess the magnitude of OCD transmission from parents to offspring, the sources of the potential familial cross-generational relationship between OCD and generalized anxiety disorder (GAD), social phobia (SP), and panic disorder (PD), and examined cross-generational genetic correlations between OCD and anxiety disorder (AD).

They conducted a population-based study analyzing data from Swedish registers that included more than 2.4 million offspring (mean age at follow-up 40.2±10.7 years; 47.8% women) born in Sweden from 1960 to 1995, lived in Sweden for at least 20 years, and stratified into 4 family types: intact, not-lived-with biological father, lived-with stepfather, and adoptive. They obtained targeted diagnoses of OCD, AD, GAD, SP, and PD from national outpatient, inpatient, and primary care medical registers, with all participants deidentified. Tetrachoric correlation (r, the correlation in relatives for a latent underlying normally distributed liability to illness) was used to evaluate parent-child resemblance.

From the total population, investigators noted 27,141 individuals (1.1%) had a lifetime diagnosis of OCD.

Investigators found the best-estimate correlation for OCD for each type of parent-child relationship examined showed rearing only, r=0.04 (95% CI, -0.10 to 0.19); genes only, 0.18 (95% CI, 0.11-0.24); and genes plus rearing, 0.19 (95% CI, 0.17-0.20). Heterogeneity tests were insignificant for genes only and genes plus rearing and not available for rearing only.

Weighted estimates from mothers and fathers for OCD-to-AD transmission showed rearing only, r=0.05 (95% CI, -0.01 to 0.12); genes only, 0.09 (95% CI, 0.05-0.13); and genes plus rearing, 0.14 (95% CI, 0.12-0.15), with no significant heterogeneity. Weighted estimates from mothers and fathers for AD-to-OCD transmission showed rearing only, 0.04 (95% CI, 0.01-0.07); genes only, 0.09 (95% CI, 0.07-0.12); and genes plus rearing, 0.13 (95% CI, 0.12-0.13) with significant heterogeneity for genes plus rearing.

Weighted estimates from mothers and fathers for AD-to-AD transmission showed rearing only, 0.07 (95% CI, 0.05-0.08); genes only, 0.12 (95% CI, 0.11-0.13); and genes plus rearing, 0.17 (95% CI, 0.17-0.17) with significant heterogeneity for genes plus rearing.

Cross-generational genetic correlations between OCD and AD diagnostic categories showed PD, 0.47 (95% CI, 0.20-0.73); SP, 0.70 (95% CI, 0.31-1.00); GAD, 0.87 (95% CI, 0.53-1.00); and all ADs, 0.62 (95% CI, 0.46-0.77) using bivariate adoption analyses.

Significant study limitations include, the observational nature of the study design, validity of results dependent upon quality of Swedish medical record diagnoses, missing data on individuals who never presented for treatment, and lacking information on mother-offspring transmission. Additional limitations include unaccounted-for parental assortative mating, treatment frequency bias, parents in the study not representative of the general Swedish population, and the inability to detect genetic influences with OCD restricted to early childhood.

“This Swedish population register-based study found that OCD was transmitted from parents to children largely through a genetic relationship, with rearing playing a minor role,” investigators concluded. They wrote “Viewed cross-generationally, OCD and anxiety disorders were moderately genetically correlated, with the genetic correlations strongest between OCD and GAD, intermediate for OCD and social phobia, and weakest between OCD and panic disorder.” When diagnostic hierarchies were applied before analysis, genetic correlations were slightly attenuated. Investigators determined transmission of OCD parent to offspring may be primarily genetic in origin and the genetic risk correlates with other AD genetic risks.