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Maternal Effects as Causes of Risk for Obsessive-Compulsive Disorder

  • Behrang Mahjani
    Affiliations
    Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, New York

    Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York

    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
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  • Lambertus Klei
    Affiliations
    Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
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  • Christina M. Hultman
    Affiliations
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
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  • Henrik Larsson
    Affiliations
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
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  • Bernie Devlin
    Affiliations
    Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
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  • Joseph D. Buxbaum
    Affiliations
    Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, New York

    Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York

    Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York

    Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York

    Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York

    Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York
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  • Sven Sandin
    Affiliations
    Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, New York

    Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York

    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
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  • Dorothy E. Grice
    Correspondence
    Address correspondence to Dorothy E. Grice, M.D., One Gustave L. Levy Place, Box 1230, New York, NY 10029.
    Affiliations
    Division of Tics, OCD, and Related Disorders, Icahn School of Medicine at Mount Sinai, New York, New York

    Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York

    Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York

    Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York
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      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.

      Keywords

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