Elsevier

Biological Psychiatry

Volume 87, Issue 12, 15 June 2020, Pages 1045-1051
Biological Psychiatry

Archival Report
Maternal Effects as Causes of Risk for Obsessive-Compulsive Disorder

https://doi.org/10.1016/j.biopsych.2020.01.006Get rights and content

Abstract

Background

While genetic variation has a known impact on the risk for obsessive-compulsive disorder (OCD), there is also evidence that there are maternal components to this risk. Here, we partitioned sources of variation, including direct genetic and maternal effects, on risk for OCD.

Methods

The study population consisted of 822,843 individuals from the Swedish Medical Birth Register, born in Sweden between January 1, 1982, and December 31, 1990, and followed for a diagnosis of OCD through December 31, 2013. Diagnostic information about OCD was obtained using the Swedish National Patient Register.

Results

A total of 7184 individuals in the birth cohort (0.87%) were diagnosed with OCD. After exploring various generalized linear mixed models to fit the diagnostic data, genetic maternal effects accounted for 7.6% (95% credible interval: 6.9%–8.3%) of the total variance in risk for OCD for the best model, and direct additive genetics accounted for 35% (95% credible interval: 32.3%–36.9%). These findings were robust under alternative models.

Conclusions

Our results establish genetic maternal effects as influencing risk for OCD in offspring. We also show that additive genetic effects in OCD are overestimated when maternal effects are not modeled.

Section snippets

Study Population

At birth, all Swedish residents are assigned a unique personal number that is used in all the national registries. Since 1973, all children born in Sweden have been recorded in the national Medical Birth Register together with birth characteristics of the children and mothers (37). The study population consists of all live-born singleton children born in Sweden between January 1, 1982, and December 31, 1990, with known father and mother as defined by the Medical Birth Register. Prospective

Results

The cohort contains 822,843 individuals, of which 7184 (0.87%) were diagnosed with OCD (60% female) using ICD-10 criteria (Table 1) followed from January 1997 through December 2013.

RRR was calculated for different relation types (Figure 1) using Cox proportional hazards regression. These analyses showed higher point estimates for maternal half-sibs compared with paternal half-sibs as well as higher RRR for maternal cousins compared with other cousins. Analysis of familial risk exhibited a

Discussion

In this cohort study of Swedish children born between January 1, 1982. and December 31, 1990, we found that genetic maternal effects contribute significantly to causes of risk for OCD. This is, to our knowledge, the first study to estimate this effect on risk for OCD and the first quantitative genetic study to identify a role for maternal effects in risk for any psychiatric disorder. Our results also demonstrate an association between parental factors and risk for OCD such as parental age,

Acknowledgments and Disclosures

This study was supported by grants from the Mindich Child Health and Development Institute (to DEG and SS), the Friedman Brain Institute (to DEG), and the Beatrice and Samuel A. Seaver Foundation (to DEG, SS, JDB, and BM), Icahn School of Medicine at Mount Sinai; the Mindworks Charitable Lead Trust (to DEG); the Stanley Center for Psychiatric Research (to DEG and JDB); and the National Institute of Mental Health (Grant No. R37MH057881 [to BD], Grant Nos. R01MH097849 and R01MH097849-S1 [to

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