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      Heritability of autism spectrum disorders: a meta-analysis of twin studies.

      Journal of Child Psychology and Psychiatry, and Allied Disciplines
      Autism spectrum disorders, DF extremes analysis, heritability, meta-analysis, twin studies

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          Abstract

          The etiology of Autism Spectrum Disorder (ASD) has been recently debated due to emerging findings on the importance of shared environmental influences. However, two recent twin studies do not support this and instead re-affirm strong genetic effects on the liability to ASD, a finding consistent with previous reports. This study conducts a systematic review and meta-analysis of all twin studies of ASD published to date and explores the etiology along the continuum of a quantitative measure of ASD.

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          Most cited references15

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          Autism as a strongly genetic disorder: evidence from a British twin study.

          Two previous epidemiological studies of autistic twins suggested that autism was predominantly genetically determined, although the findings with regard to a broader phenotype of cognitive, and possibly social, abnormalities were contradictory. Obstetric and perinatal hazards were also invoked as environmentally determined aetiological factors. The first British twin sample has been re-examined and a second total population sample of autistic twins recruited. In the combined sample 60% of monozygotic (MZ) pairs were concordant for autism versus no dizygotic (DZ) pairs; 92% of MZ pairs were concordant for a broader spectrum of related cognitive or social abnormalities versus 10% of DZ pairs. The findings indicate that autism is under a high degree of genetic control and suggest the involvement of multiple genetic loci. Obstetric hazards usually appear to be consequences of genetically influenced abnormal development, rather than independent aetiological factors. Few new cases had possible medical aetiologies, refuting claims that recognized disorders are common aetiological influences.
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            Heritability of Autism Spectrum Disorder in a UK Population-Based Twin Sample.

            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. 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. 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). 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. 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%]). 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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              Autism diagnostic observation schedule: a standardized observation of communicative and social behavior.

              The Autism Diagnostic Observation Schedule (ADOS), a standardized protocol for observation of social and communicative behavior associated with autism, is described. The instrument consists of a series of structured and semistructured presses for interaction, accompanied by coding of specific target behaviors associated with particular tasks and by general ratings of the quality of behaviors. Interrater reliability for five raters exceeded weighted kappas of .55 for each item and each pair of raters for matched samples of 15 to 40 autistic and nonautistic, mildly mentally handicapped children (M IQ = 59) between the ages of 6 and 18 years. Test-retest reliability was adequate. Further analyses compared these groups to two additional samples of autistic and nonautistic subjects with normal intelligence (M IQ = 95), matched for sex and chronological age. Analyses yielded clear diagnostic differences in general ratings of social behavior, specific aspects of communication, and restricted or stereotypic behaviors and interests. Clinical guidelines for the diagnosis of autism in the draft version of ICD-10 were operationalized in terms of abnormalities on specific ADOS items. An algorithm based on these items was shown to have high reliability and discriminant validity.
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                Author and article information

                Journal
                26709141
                10.1111/jcpp.12499

                Autism spectrum disorders,DF extremes analysis,heritability,meta-analysis,twin studies

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