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Heritability of Autism Spectrum Disorder in a UK Population-Based Twin Sample

自闭症 自闭症谱系障碍 孤独症诊断观察量表 人口 遗传力 双胞胎研究 心理学 队列 范畴变量 医学 发展心理学 统计 遗传学 生物 数学 环境卫生 内科学
作者
Emma Colvert,Beata Tick,Fiona McEwen,Catherine Stewart,Sarah Curran,Emma Woodhouse,Nicola Gillan,Victoria Hallett,Stephanie Lietz,Tracy Garnett,Angelica Ronald,Robert Plomin,Frühling Rijsdijk,Francesca Happé,Patrick Bolton
出处
期刊:JAMA Psychiatry [American Medical Association]
卷期号:72 (5): 415-415 被引量:375
标识
DOI:10.1001/jamapsychiatry.2014.3028
摘要

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.
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