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JAMA Psychiatry. 2015 May;72(5):415-23. doi: 10.1001/jamapsychiatry.2014.3028.

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

Author information

1
MRC Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, England.
2
MRC Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, England2Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology, and Neuroscience, K.
3
South London and Maudsley NHS (National Health Service) Foundation Trust, Maudsley Hospital, London, England4Department of Psychology, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, England.
4
Department of Psychology, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, England5Brighton and Sussex Medical School, University of Sussex, East Sussex, England6Sussex Partnership NHS Foundation Trust, Trust Headquart.
5
Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, England.
6
South London and Maudsley NHS (National Health Service) Foundation Trust, Maudsley Hospital, London, England.
7
Department of Psychology, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, England.
8
Research Department of Clinical, Educational and Health Psychology, University College London, London, England.
9
MRC Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, England9Department of Psychological Sciences, University of London, London, England.

Abstract

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.

PMID:
25738232
PMCID:
PMC4724890
DOI:
10.1001/jamapsychiatry.2014.3028
[Indexed for MEDLINE]
Free PMC Article

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