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.
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Biol Psychiatry. 2020 Jun 15;87(12):1045-1051. doi: 10.1016/j.biopsych.2020.01.006. Epub 2020 Jan 22.
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.
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.
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.
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.
虽然遗传变异对强迫症（OCD）的风险有已知的影响，但也有证据表明这种风险存在母体成分。在这里，我们将变异的来源（包括直接遗传和母体效应）进行了划分，以确定 OCD 的风险因素。
研究人群包括 1982 年 1 月 1 日至 1990 年 12 月 31 日期间在瑞典出生的 822843 名个体，他们在瑞典出生，通过瑞典国家患者登记册对 OCD 进行诊断，并在 2013 年 12 月 31 日之前进行随访。关于 OCD 的诊断信息是通过瑞典国家患者登记册获得的。
在出生队列中，共有 7184 人（0.87%）被诊断患有 OCD。在探索了各种广义线性混合模型以拟合诊断数据后，对于最佳模型，遗传母体效应占 OCD 风险总方差的 7.6%（95%可信区间：6.9%-8.3%），直接加性遗传占 35%（95%可信区间：32.3%-36.9%）。在替代模型下，这些发现是稳健的。
我们的研究结果确立了遗传母体效应对后代 OCD 风险的影响。我们还表明，当未对母体效应进行建模时，OCD 中的加性遗传效应会被高估。
