Behrang Mahjani1, Lambertus Klei2, Christina M Hultman3, Henrik Larsson3, Bernie Devlin2, Joseph D Buxbaum4, Sven Sandin1, Dorothy E Grice5. 1. 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. 2. Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. 3. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. 4. 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. 5. 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. Electronic address: dorothy.grice@mssm.edu.
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. Published by Elsevier Inc.
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. Published by Elsevier Inc.
Entities:
Keywords:
Assortative mating; Direct genetic effects; Heritability; Maternal effects; Obsessive-compulsive disorder; Population based
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