BACKGROUND Autism spectrum disorder (ASD) has both genetic and environmental origins, including potentially maternal effects. Maternal effects describe the association of one or more maternal phenotypes with liability to ASD in progeny that are independent of maternally transmitted risk alleles. While maternal effects could play an important role, consistent with association to maternal traits such as immune status, no study has estimated maternal, additive genetic, and environmental effects in ASD. METHODS Using a population-based sample consisting of all children born in Sweden from 1998 to 2007 and their relatives, we fitted statistical models to family data to estimate the variance in ASD liability originating from maternal, additive genetic, and shared environmental effects. We calculated sibling and cousin family recurrence risk ratio as a direct measure of familial, genetic, and environmental risk factors and repeated the calculations on diagnostic subgroups, specifically autistic disorder (AD) and spectrum disorder (SD), which included Asperger’s syndrome and/or pervasive developmental disorder not otherwise specified. RESULTS The sample consisted of 776,212 children of whom 11,231 had a diagnosis of ASD: 4554 with AD, 6677 with SD. We found support for large additive genetic contribution to liability; heritability (95% confidence interval [CI]) was estimated to 84.8% (95% CI: 73.1–87.3) for ASD, 79.6% (95% CI: 61.2–85.1) for AD, and 76.4% (95% CI: 63.0–82.5) for SD. CONCLUSIONS There was modest, if any, contribution of maternal effects to liability for ASD, including subtypes AD and SD, and there was no support for shared environmental effects. These results show liability to ASD arises largely from additive genetic variation.

中文翻译：

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瑞典自闭症谱系障碍复发风险的遗传变异，很少或没有母体遗传贡献

背景自闭症谱系障碍（ASD）具有遗传和环境起源，包括潜在的母体影响。母体效应描述了一种或多种母体表型与后代中 ASD 易感性的关联，这些表型与母体传播的风险等位基因无关。虽然母体效应可能发挥重要作用，与免疫状态等母体特征的关联一致，但没有研究估计 ASD 中的母体、附加遗传和环境影响。方法 使用由 1998 年至 2007 年在瑞典出生的所有儿童及其亲属组成的基于人群的样本，我们将统计模型拟合到家庭数据中，以估计源自母体、附加遗传和共享环境影响的 ASD 责任方差。我们计算了兄弟姐妹和表亲家庭复发风险比作为家族、遗传和环境风险因素的直接衡量标准，并重复了对诊断亚组的计算，特别是自闭症 (AD) 和谱系障碍 (SD)，其中包括阿斯伯格综合症和/或未另作说明的广泛性发育障碍。结果 样本包括 776,212 名儿童，其中 11,231 名被诊断为 ASD：4554 名患有 AD，6677 名患有 SD。我们发现了对责任的大量附加遗传贡献的支持；ASD 的遗传力（95% 置信区间 [CI]）估计为 84.8%（95% CI：73.1-87.3），AD 为 79.6%（95% CI：61.2-85.1），76.4%（95% CI：63.0） –82.5) 用于 SD。结论 母体效应对 ASD 责任的贡献不大（如果有的话），包括亚型 AD 和 SD，并且不支持共享环境影响。这些结果表明 ASD 的倾向主要来自于加性遗传变异。