Association of Genetic and Environmental Factors With Autism in a 5-Country Cohort
Association of Genetic and Environmental Factors With Autism in a 5-Country Cohort
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DOI：
10.1001/jamapsychiatry.2019.1411
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发表时间：
2019-10-01
期刊：
影响因子：
25.8
通讯作者：
Sandin, Sven
中科院分区：
文献类型：
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作者：
Bai, Dan;Yip, Benjamin Hon Kei;Sandin, Sven
自闭症谱系障碍（ASD）的起源和发展仍未得到解决。没有个体水平的研究提供了几个国家中ASD的遗传、母体和环境影响的估计。目的探讨遗传、母体和环境因素对ASD的影响。设计、环境和参与者：以人群为基础的多国队列研究，包括1998年1月1日至2011年12月31日期间出生的丹麦、芬兰、瑞典、以色列和西澳大利亚的儿童的完整出生队列，随访至16岁。数据分析时间为2016年9月23日至2018年2月4日。在5个国家中，我们拟合了模型来估计描述由于加性遗传、母体以及共有和非共有环境影响而导致的ASD发生风险总方差的方差成分。结果共纳入2001631例，其中男性1027546例，占51.3%。在整个样本中，22156人被诊断为ASD。国家特定点估计的ASD遗传率中位数（95% CI）为80.8%(73.2%-85.5%)，范围从50.9%(25.1%-75.6%)（芬兰）到86.8%(69.8%-100.0%)（以色列）。对于北欧国家，遗传率估计从81.2%（73.9%-85.3%）到82.7%（79.1%-86.0%）不等。母亲的影响估计在0.4%到1.6%之间。对自闭症的遗传、母体和环境影响的估计与ASD相似。结论和相关性基于5个国家的人群数据，ASD的遗传率估计约为80%，表明人群中ASD发生的差异主要是由于遗传的影响，而不是来自母亲的影响。研究结果表明，不同国家之间的自闭症风险来源可能存在适度差异。
IMPORTANCE The origins and development of autism spectrum disorder (ASD) remain unresolved. No individual-level study has provided estimates of additive genetic, maternal, and environmental effects in ASD across several countries.OBJECTIVE To estimate the additive genetic, maternal, and environmental effects in ASD.DESIGN, SETTING, AND PARTICIPANTS Population-based, multinational cohort study including full birth cohorts of children from Denmark, Finland, Sweden, Israel, and Western Australia born between January 1, 1998, and December 31, 2011, and followed up to age 16 years. Data were analyzed from September 23, 2016 through February 4, 2018.MAIN OUTCOMES AND MEASURES Across 5 countries, models were fitted to estimate variance components describing the total variance in risk for ASD occurrence owing to additive genetics, maternal, and shared and nonshared environmental effects.RESULTS The analytic sample included 2001631 individuals, of whom 1027546 (51.3%) were male. Among the entire sample, 22156 were diagnosed with ASD. The median (95% CI) ASD heritability was 80.8% (73.2%-85.5%) for country-specific point estimates, ranging from 50.9% (25.1%-75.6%) (Finland) to 86.8% (69.8%-100.0%) (Israel). For the Nordic countries combined, heritability estimates ranged from 81.2% (73.9%-85.3%) to 82.7% (79.1%-86.0%). Maternal effect was estimated to range from 0.4% to 1.6%. Estimates of genetic, maternal, and environmental effects for autistic disorder were similar with ASD.CONCLUSIONS AND RELEVANCE Based on population data from 5 countries, the heritability of ASD was estimated to be approximately 80%, indicating that the variation in ASD occurrence in the population is mostly owing to inherited genetic influences, with no support for contribution from maternal effects. The results suggest possible modest differences in the sources of ASD risk between countries.