Heritability of Autism Spectrum Disorder in a UK Population-Based Twin Sample
Heritability of Autism Spectrum Disorder in a UK Population-Based Twin Sample
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DOI：
10.1001/jamapsychiatry.2014.3028
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发表时间：
2015-05-01
期刊：
影响因子：
25.8
通讯作者：
Bolton, Patrick
中科院分区：
文献类型：
--
作者：
Colvert, Emma;Tick, Beata;Bolton, Patrick
重要性 迄今为止的大多数证据都强调了遗传影响对自闭症和相关特征的重要性。然而，这些发现大部分来自临床确定的样本，可能缺少表现更微妙的个体，并且获得的估计值可能不能代表总体。 目的 在基于大量人群的双胞胎样本中确定遗传和环境因素对自闭症谱系障碍 (ASD) 和更广泛的自闭症表型的相对贡献，并确定维度特征测量和分类诊断之间的遗传/环境关系 ASD 的构建、设计、设置和参与者 我们使用了基于人群的双胞胎早期发育研究的数据，其中包括 1994 年 1 月 1 日至 1996 年 12 月 31 日在英格兰和威尔士出生的所有双胞胎。我们使用全信息最大似然法进行联合连续顺序责任阈值模型拟合，以估计协方差的遗传和环境参数。双胞胎接受了以下评估：儿童自闭症谱系测试（CAST）（6423 对；平均年龄，7.9 岁）、发育和健康评估（DAWBA）（359 对；平均年龄，10.3 岁）、自闭症诊断观察表（ADOS）（203 对；平均年龄，13.2 岁）、自闭症诊断访谈修订版（ADI-R） （205对； 平均年龄，13.2 岁）和最佳估计诊断（207 对）。 主要结果和测量 参与者使用基于人群的自闭症特征测量（CAST 评估）、结构化诊断评估（DAWBA、ADI-R 和 ADOS）和最佳估计诊断进行筛查。 结果 在所有 ASD 测量中，同卵双胞胎之间的相关性（范围、 0.77-0.99）显着高于异卵双胞胎（范围，0.22-0.65），遗传力估计为 56% 至 95%。 CAST 和 ASD 诊断状态（DAWBA、ADOS 和最佳估计诊断）的协方差很大程度上是由附加遗传因素（76%-95%）解释的。仅对于 ADI-R，共同的环境影响很显着（30% [95% CI, 8%-47%]），但小于遗传影响（56% [95% CI, 37%-82%]）。结论和相关性 在这个基于人群的大型双胞胎样本中，自闭症谱系障碍和更广泛定义的高水平自闭症特征表型主要源自加性遗传，并且在较小程度上， 非共享环境影响。不同诊断工具的结果基本一致，表明结果可以推广到多种测量和评估方法。支撑自闭症样特征个体差异的遗传因素与诊断自闭症谱系障碍的遗传影响有相当大的重叠。
IMPORTANCE Most evidence to date highlights the importance of genetic influences on the liability to autism and related traits. However, most of these findings are derived from clinically ascertained samples, possibly missing individuals with subtler manifestations, and obtained estimates may not be representative of the population.OBJECTIVES To establish the relative contributions of genetic and environmental factors in liability to autism spectrum disorder (ASD) and a broader autism phenotype in a large population-based twin sample and to ascertain the genetic/environmental relationship between dimensional trait measures and categorical diagnostic constructs of ASD.DESIGN, SETTING, AND PARTICIPANTS We used data from the population-based cohort Twins Early Development Study, which included all twin pairs born in England and wales from January 1, 1994, through December 31, 1996. We performed joint continuous-ordinal liability threshold model fitting using the full information maximum likelihood method to estimate genetic and environmental parameters of covariance. Twin pairs underwent the following assessments: the Childhood Autism Spectrum Test (CAST) (6423 pairs; mean age, 7.9 years), the Development and Well-being Assessment (DAWBA) (359 pairs; mean age, 10.3 years), the Autism Diagnostic Observation Schedule (ADOS) (203 pairs; mean age, 13.2 years), the Autism Diagnostic Interview-Revised (ADI-R) (205 pairs; mean age, 13.2 years), and a best-estimate diagnosis (207 pairs).MAIN OUTCOMES AND MEASURES Participants underwent screening using a population-based measure of autistic traits (CAST assessment), structured diagnostic assessments (DAWBA, ADI-R, and ADOS), and a best-estimate diagnosis.RESULTS On all ASD measures, correlations among monozygotic twins (range, 0.77-0.99) were significantly higher than those for dizygotic twins (range, 0.22-0.65), giving heritability estimates of 56% to 95%. The covariance of CAST and ASD diagnostic status (DAWBA, ADOS and best-estimate diagnosis) was largely explained by additive genetic factors (76%-95%). For the ADI-R only, shared environmental influences were significant (30% [95% CI, 8%-47%]) but smaller than genetic influences (56% [95% CI, 37%-82%]).CONCLUSIONS AND RELEVANCE The liability to ASD and a more broadly defined high-level autism trait phenotype in this large population-based twin sample derives primarily from additive genetic and, to a lesser extent, nonshared environmental effects. The largely consistent results across different diagnostic tools suggest that the results are generalizable across multiple measures and assessment methods. Genetic factors underpinning individual differences in autismlike traits show considerable overlap with genetic influences on diagnosed ASD.