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Cited by 560Autism Spectrum Disorder ResearchGenetics and Neurodevelopmental DisordersGenetic Associations and Epidemiology

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

Open access
Colvert, Emma, Tick, Beata, McEwen, Fiona, Stewart, Catherine, Curran, Sarah R., Woodhouse, Emma, Gillan, Nicola, Hallett, Victoria +7 more·2015·JAMA Psychiatry
DOI 10.1001/jamapsychiatry.2014.3028PMC PMC4724890
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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.

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Crossref · 10.1001/jamapsychiatry.2014.3028

Cites

59 of 59 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 44 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Agreement between diagnostic measures was moderate to almost perfect, with weighted kappa values from 0.58 to 0.91.

    “We found moderate κ agreement for DAWBA and the ADOS assessment (0.58) and substantial agreement for DAWBA and the ADI-R assessment and for DAWBA and BeD (both 0.72), for the ADI-R and ADOS assessments (0.67), and for the ADOS assessment and BeD (0.79). Agreement for the ADI-R assessment and BeD was almost perfect (0.91).”
    Quote in the paperNot a substantial claim
  • Findingown data

    Shared environmental influences significantly explained variance in ADI-R only (30% [95% CI, 8%-47%]).

    “Genetic influences were significant for all clinical measures with the highest heritability reported for BeD (95% [95% CI, 74%-98%]) and shared environments significantly explaining the variance of the ADI-R assessment only (30% [95% CI, 8%-47%]).”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: The liability to ASD and a broader autism phenotype follows a continuous distribution.
    • The authors state this as an assumption: CAST scores and the three ASD diagnostic categories follow a joint multivariate normal distribution.
  • Findingown data

    Genetic correlations between CAST and clinical measures were substantial (0.52-0.89).

    “The genetic correlations, that is, the extent to which the same genetic factors influence the CAST score and clinical measures independent of their heritabilities, are substantial (0.52-0.89).”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: The liability to ASD and a broader autism phenotype follows a continuous distribution.
    • The authors state this as an assumption: CAST scores and the three ASD diagnostic categories follow a joint multivariate normal distribution.
  • Findingown data

    Significant shared environment effects appeared only for the ADI-R developmental history measure reported by parents.

    “In our study, only the ADI-R parent-reported developmental history measure showed significant shared environment effects.”
    Quote in the paperSubstantial claim
  • Findingown data

    Covariance between CAST and ASD diagnostic status (DAWBA, ADOS, BeD) was largely explained by additive genetic factors (76%-95%).

    “The covariance of CAST and ASD diagnostic status (DAWBA, ADOS and best-estimate diagnosis) was largely explained by additive genetic factors (76%-95%).”
    Quote in the paperSubstantial claim
  • May combine two claims. 27
  • Classified as probably not a substantial claim. 14
  • The quote only partly states this claim. 1

  • May combine two claims.

    Findingown data

    MZ concordance is 0.87 for ASD and 0.94 for BeD, vs DZ 0.22 and 0.46.

    “For example, MZ concordances are 0.87 for ASD and 0.94 for BeD, in contrast to 0.22 and 0.46, respectively, for DZ concordances.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    All clinical measures showed significant genetic effects; BeD had the highest heritability (95% [95% CI, 74%-98%]).

    “Genetic influences were significant for all clinical measures with the highest heritability reported for BeD (95% [95% CI, 74%-98%]) and shared environments significantly explaining the variance of the ADI-R assessment only (30% [95% CI, 8%-47%]).”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: The liability to ASD and a broader autism phenotype follows a continuous distribution.
    • The authors state this as an assumption: CAST scores and the three ASD diagnostic categories follow a joint multivariate normal distribution.

  • May combine two claims.

    Findingown data

    Remainder of covariance between CAST and ASD measures was explained by nonshared environmental factors, though nonsignificant for CAST-ADI-R and CAST-ADOS overlap.

    “The remainder of the covariance was explained by non-shared environmental factors (rph_E), although nonsignificant for the overlap between the CAST score and the ADI-R or the ADOS assessment.”
    Quote in the paperNot a substantial claim
    • The authors state this as an assumption: The liability to ASD and a broader autism phenotype follows a continuous distribution.
    • The authors state this as an assumption: CAST scores and the three ASD diagnostic categories follow a joint multivariate normal distribution.

  • May combine two claims.

    Findingcitation

    Variance in CAST score (age and sex regressed) was 78% genetic (95% CI 77-79) and 22% nonshared environmental (95% CI 21-23).

    “Variance in the CAST score (age and sex regressed) resulted from genetic influences (78% [95% CI, 77%-79%]) and nonshared environmental effects (22% [95% CI, 21%-23%]), as reported previously.30”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [30] Ronald A Happé F Bolton P Genetic heterogeneity between the three components of the autism spectrum: a twin study J Am Acad Child Adolesc Psychiatry 2006 45 6 691 699 16721319

      Not checked in the free run.

    • The authors state this as an assumption: The liability to ASD and a broader autism phenotype follows a continuous distribution.
    • The authors state this as an assumption: CAST scores and the three ASD diagnostic categories follow a joint multivariate normal distribution.

  • May combine two claims.

    Findingown data

    Phenotypic correlations between CAST and each ASD variable were moderate to high (0.52-0.65), and genetic factors accounted for 77%-100% of covariance.

    “The phenotypic correlations were moderate to high (0.52-0.65), and genetic factors accounted for 77% to 100% of the covariance.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: The liability to ASD and a broader autism phenotype follows a continuous distribution.
    • The authors state this as an assumption: CAST scores and the three ASD diagnostic categories follow a joint multivariate normal distribution.

  • May combine two claims.

    Findingown data

    Probandwise concordance rates ranged 0.62-0.94 in MZ twins and 0.05-0.61 in DZ twins.

    “The high MZ (0.62-0.94) and low DZ (0.05-0.61) concordances suggest substantial genetic influence.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    For ADI-R only, shared environmental influences were significant (30% [95% CI, 8%-47%]) but smaller than genetic influences (56% [95% CI, 37%-82%]).

    “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%]).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Relationship between CAST and diagnostic assessments indicated substantial genetic correlation and significant nonshared environmental correlation.

    “Indeed, the relationship between the CAST score and diagnostic assessments indicated a substantial genetic correlation and a significant correlation in the nonshared environmental factors that influence variations in both traits.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Twin and family studies show genetic liability to autism confers risk for broader impairments in social communication, restricted/repetitive behaviors, and behaviors beyond traditional diagnostic boundaries.

    “Twin and family studies21,22 have also shown that the genetic liability to autism confers a risk for a broader range of impairments in social communication, restricted and repetitive behaviors, and behaviors that extend beyond the traditional diagnostic boundaries for autism.9,23,24”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [21] Bishop DVM Maybery M Wong D Maley A Hallmayer J Characteristics of the broader phenotype in autism: a study of siblings using the Children’s Communication Checklist-2 Am J Med Genet B Neuropsychiatr Genet 2006 141B 2 117 122 16389586

      Not checked in the free run.

    • cites [22] Constantino JN Todorov A Hilton C Autism recurrence in half siblings: strong support for genetic mechanisms of transmission in ASD Mol Psychiatry 2013 18 2 137 138 22371046

      Not checked in the free run.

    • cites [9] Ronald A Hoekstra RA Autism spectrum disorders and autistic traits: a decade of new twin studies Am J Med Genet B Neuropsychiatr Genet 2011 156B 3 255 274 21438136

      Not checked in the free run.

    • cites [23] Sucksmith E Roth I Hoekstra RA Autistic traits below the clinical threshold: re-examining the broader autism phenotype in the 21st century Neuropsychol Rev 2011 21 4 360 389 21989834

      Not checked in the free run.

    • cites [24] Pickles A Starr E Kazak S Variable expression of the autism broader phenotype: findings from extended pedigrees J Child Psychol Psychiatry 2000 41 4 491 502 10836679

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A molecular genetic study found that common allelic variants explain 95% of ASD variance, which supports a polygenic model.

    “Most recently, in the same population, molecular genetic analysis19 indicated that 95% of variance in ASD is accounted for by common allelic variants, supporting a polygenic model.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [19] Gaugler T Klei L Sanders SJ Most genetic risk for autism resides with common variation Nat Genet 2014 46 8 881 885 25038753 PMC4137411

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    Of 412 eligible families at stage 1, 80.1% completed the DAWBA interview.

    “Of the 412 eligible families for the Social Relationship Study at stage 1, 80.1% completed the Development and Well-being Assessment (DAWBA) interview.34,35”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [34] Dworzynski K Happé F Bolton P Ronald A Relationship between symptom domains in autism spectrum disorders: a population based twin study J Autism Dev Disord 2009 39 8 1197 1210 19373549

      Not checked in the free run.

    • cites [35] Goodman R Ford T Richards H Gatward R Meltzer H The Development and Well-Being Assessment: description and initial validation of an integrated assessment of child and adolescent psychopathology J Child Psychol Psychiatry 2000 41 5 645 655 10946756

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Two twin studies reported moderate heritability (21%-38%) and substantial shared environmental component (58%-78%) for ASD liability.

    “Two twin studies15,16 stand in contrast and reported only moderate heritability (21%-38%), with a substantial shared environmental component explaining 58% to 78% of the variance in liability to autism spectrum disorder (ASD).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [15] Hallmayer J Cleveland S Torres A Genetic heritability and shared environmental factors among twin pairs with autism Arch Gen Psychiatry 2011 68 11 1095 1102 21727249 PMC4440679

      Not checked in the free run.

    • cites [16] Frazier TW Thompson L Youngstrom EA A twin study of heritable and shared environmental contributions to autism J Autism Dev Disord 2014 44 8 2013 2025 24604525 PMC4104233

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    A large extended-family population study (~2 million) reported 50% heritability and nonshared environmental factors.

    “In addition, a large population study of extended families (approximately 2 million individuals)18 reported estimates of 50% for heritability and nonshared environmental factors.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [18] Sandin S Lichtenstein P Kuja-Halkola R Larsson H Hultman CM Reichenberg A The familial risk of autism JAMA 2014 311 17 1770 1777 24794370 PMC4381277

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The ADI-R is an established instrument for diagnosing autism.

    “The ADI-R is a well-established diagnostic tool for the assessment of autism.36”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [36] Lord C Rutter M Le Couteur A Autism Diagnostic Interview-Revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders J Autism Dev Disord 1994 24 5 659 685 7814313

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The 2:1 MZ:DZ ratio of cross-twin within-trait correlations for ADOS and BeD suggests significant genetic effects with remainder nonshared environmental.

    “The 2:1 MZ:DZ ratio of the cross-twin within-trait correlations for the ADOS assessment and BeD suggest a significant contribution of genetic effects, with the remainder explained by nonshared environmental effects (Table 2).”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Investigators assigning best-estimate diagnoses did not know zygosity or the co-twin's diagnostic status.

    “Diagnoses were assigned with investigators blinded to zygosity and co-twin diagnostic status after review of all available information (ADI-R, ADOS, and DAWBA assessments and clinical reports).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Reviews agree that MZ concordance for autism is typically at least twice DZ concordance, yielding high heritability estimates (60%-90%) and suggesting little shared environmental influence.

    “Recent reviews of this literature5,7-9 show general agreement across studies that concordance for autism in monozygotic (MZ) twin pairs is typically at least double that in dizygotic (DZ) twin pairs, resulting in high heritability estimates (60%-90%)10-14 and suggesting little influence of shared environmental factors.”
    Quote in the paperSubstantial claim0 of 9 sources checked
    • cites [5] Bailey A Le Couteur A Gottesman I Autism as a strongly genetic disorder: evidence from a British twin study Psychol Med 1995 25 1 63 77 7792363

      Not checked in the free run.

    • cites [7] Taniai H Nishiyama T Miyachi T Imaeda M Sumi S Genetic influences on the broad spectrum of autism: study of proband-ascertained twins Am J Med Genet B Neuropsychiatr Genet 2008 147B 6 844 849 18361421

      Not checked in the free run.

    • cites [8] Rosenberg RE Daniels AM Law JK Law PA Kaufmann WE Trends in autism spectrum disorder diagnoses: 1994-2007 J Autism Dev Disord 2009 39 8 1099 1111 19294498

      Not checked in the free run.

    • cites [9] Ronald A Hoekstra RA Autism spectrum disorders and autistic traits: a decade of new twin studies Am J Med Genet B Neuropsychiatr Genet 2011 156B 3 255 274 21438136

      Not checked in the free run.

    • cites [10] Ronald A Happé F Plomin R The genetic relationship between individual differences in social and nonsocial behaviours characteristic of autism Dev Sci 2005 8 5 444 458 16048517

      Not checked in the free run.

    • cites [11] Ronald A Happé F Price TS Baron-Cohen S Plomin R Phenotypic and genetic overlap between autistic traits at the extremes of the general population J Am Acad Child Adolesc Psychiatry 2006 45 10 1206 1214 17003666

      Not checked in the free run.

    • cites [12] Ronald A Happé F Plomin R A twin study investigating the genetic and environmental aetiologies of parent, teacher and child ratings of autistic-like traits and their overlap Eur Child Adolesc Psychiatry 2008 17 8 473 483 18427861

      Not checked in the free run.

    • cites [13] Skuse DH Mandy WPL Scourfield J Measuring autistic traits: heritability, reliability and validity of the Social and Communication Disorders Checklist Br J Psychiatry 2005 187 568 572 16319410

      Not checked in the free run.

    • cites [14] Hoekstra RA Bartels M Verweij CJ Boomsma DI Heritability of autistic traits in the general population Arch Pediatr Adolesc Med 2007 161 4 372 377 17404134

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The ADOS is a validated observational measure intended for use alongside the ADI-R when diagnosing ASD.

    “The ADOS is a well-validated, semistructured observational assessment designed to accompany the ADI-R in the diagnosis of ASD.37”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [37] Lord C Rutter M Goode S Autism Diagnostic Observation Schedule: a standardized observation of communicative and social behavior J Autism Dev Disord 1989 19 2 185 212 2745388

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    CAST cutoff ≥15 has reported 100% sensitivity, 97% specificity, and 50% PPV for ASD diagnosis.

    “a cutoff score of 15 or greater is reported to have 100% sensitivity, 97% specificity, and a positive predictive value of 50% for a diagnosis of ASD.28”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [28] Williams J Scott F Stott C The CAST (Childhood Asperger Syndrome Test): test accuracy Autism 2005 9 1 45 68 15618262

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductown data

    In 89 cases, diagnostic classifications were inconsistent; expert clinicians assigned best-estimate diagnoses after reviewing all data.

    “In 89 cases, the diagnostic classifications across instruments were inconsistent. In these cases, all available data were assessed by expert clinicians (E.C., S.R.C., and/or P.B.), and best-estimate diagnoses (BeDs) were assigned based on this review.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Shared environmental factors were modeled on ASD only because they do not influence CAST variance and cannot explain covariance with ASD.

    “Shared environmental factors were modeled on ASD only; they do not influence the variance of the CAST scores46 and therefore cannot explain the covariance with ASD.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [46] Holmboe K Rijsdijk FV Hallett V Happé F Plomin R Ronald A Strong genetic influences on the stability of autistic traits in childhood J AmAcad Child Adolesc Psychiatry 2014 53 2 221 230 PMC3919213 24472256

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    The present study used criterion-standard, in-person clinical diagnostic tools with a population-based sample and good ascertainment (62.1% response vs 17% in Hallmayer et al).

    “Our study is novel in using criterion-standard, in-person, clinical diagnostic tools with a population-based (vs a clinic-based) sample in which ascertainment was good (62.1% response rate from the eligible sample compared with 17% in the study by Hallmayer et al15).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [15] Hallmayer J Cleveland S Torres A Genetic heritability and shared environmental factors among twin pairs with autism Arch Gen Psychiatry 2011 68 11 1095 1102 21727249 PMC4440679

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Stage 2 diagnostic evaluations were completed by 62.1% of the 235 eligible families.

    “At stage 2, 62.1% of the 235 eligible families underwent diagnostic evaluations.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisereasoning

    Previous twin studies identified samples through clinical services, which could cause sampling bias; if participation is influenced by concordance, DZ probandwise concordance might be increased, inflating shared environmental estimates.

    “Previous studies15,16 have identified their twin samples through clinical services. Such a strategy could result in sampling bias; if registration or participation is influenced by concordance, probandwise concordance rates in DZ twin pairs might be increased, resulting in inflated estimates of common environmental influence.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [15] Hallmayer J Cleveland S Torres A Genetic heritability and shared environmental factors among twin pairs with autism Arch Gen Psychiatry 2011 68 11 1095 1102 21727249 PMC4440679

      Not checked in the free run.

    • cites [16] Frazier TW Thompson L Youngstrom EA A twin study of heritable and shared environmental contributions to autism J Autism Dev Disord 2014 44 8 2013 2025 24604525 PMC4104233

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Among high-CAST/suspected ASD group, 36.4% were female vs 16.6% of final sample.

    “Among the group with high CAST scores or suspected ASD, 36.4% were female compared with 16.6% of the final sample.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    A recent twin investigation found no significant shared environmental effects and estimated heritability at 95%.

    “In comparison, 1 recent twin study did not confirm significant shared environmental effects and reported heritability of 95%.17”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [17] Nordenbæk C Jørgensen M Kyvik KO Bilenberg N A Danish population-based twin study on autism spectrum disorders Eur Child Adolesc Psychiatry 2014 23 1 35 43 23661220

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    Different assessors administered ADI-R and ADOS within each twin pair to minimize rater bias.

    “This design meant that different assessors administered the ADI-R and ADOS assessments within each pair to minimize any effects of rater bias.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductnone given

    The TEDS sample is considered representative of the UK population in maternal ethnicity (92.8% white) and education (40.1% with A level or higher).

    “The Twins Early Development Study sample is considered representative of the population of the United Kingdom in terms of maternal ethnicity (92.8% white) and educational level (40.1% with A level qualifications or higher, the equivalent of some college education in the United States).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Additive genetic factors explained most ASD liability, with a smaller share from nonshared environment, and this pattern was consistent across measures.

    “Analyses partitioning liability into genetic and shared and nonshared environmental components indicate that most liability could be attributed to additive genetic influences and a smaller proportion attributed to non-shared environmental influences. This finding held across a number of different measures.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: The liability to ASD and a broader autism phenotype follows a continuous distribution.
    • The authors state this as an assumption: CAST scores and the three ASD diagnostic categories follow a joint multivariate normal distribution.

  • May combine two claims.

    Interpretationown data

    The results support strong genetic effects in ASD and little shared environmental influence.

    “Our findings are broadly in line with those of recent twin and family studies and point toward strong genetic effects in ASD and no strong influence from shared environmental factors.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Including subclinical high-trait cases yields high ASD heritability, which supports the idea that genetic risk for autism extends to a broader phenotype.

    “Our findings also confirm that the heritability of the liability to ASD is high when incorporating subclinical cases with high trait scores into the model, extending support for the notion that the genetic liability to autism confers a risk for a broader autism phenotype.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    The finding suggests shared etiology for autistic trait variation across the full spectrum and across the three clinical categories.

    “This result indicates common etiologic underpinnings for individual differences in autistic traits across the whole spectrum and in our 3 clinically meaningful categories (ASD, high subclinical trait level, and low risk/trait level).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    In UK twins aged 8 years and older, ASD liability and a broader high-level autism trait phenotype are mainly influenced by genetic factors, with a moderate nonshared environmental contribution.

    “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.”
    • Also stated in: § Conclusions · plain
      “We conclude that liability to ASD and a more broadly defined high-level autism trait phenotype in UK twins 8 years or older derives from substantial genetic and moderate nonshared environmental influences.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: The liability to ASD and a broader autism phenotype follows a continuous distribution.
    • The authors state this as an assumption: CAST scores and the three ASD diagnostic categories follow a joint multivariate normal distribution.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). The quote only partly states this claim.

    Study design and conductnone given

    To our knowledge, no larger screened population-based twin study has been reported.

    “In addition, to the best of our knowledge, this study is one of the largest screened population-based twin studies yet reported.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given

    Heritability values apply to a given population and change with the prevailing environment.

    “Heritability estimates are also population specific and depend on the dynamic interaction with the current environment.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    There was very little evidence of shared environmental effects overall, contrary to Hallmayer et al, though wide CIs overlap with some present estimates.

    “We found very little evidence of shared environmental effects overall, which is contrary to the findings of Hallmayer et al,15 although the wide CIs in their results for additive genetic and shared environmental effects overlap with some of the present estimates.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [15] Hallmayer J Cleveland S Torres A Genetic heritability and shared environmental factors among twin pairs with autism Arch Gen Psychiatry 2011 68 11 1095 1102 21727249 PMC4440679

      Not checked in the free run.

36 of 36

  • The authors state this as an assumption.

    The liability to ASD and a broader autism phenotype follows a continuous distribution.

    “we assumed a continuous liability distribution underlying ASD and a more broadly defined phenotype with high-level autism traits that fell short of thresholds for an ASD diagnosis.”

  • The authors state this as an assumption.

    CAST scores and the three ASD diagnostic categories follow a joint multivariate normal distribution.

    “The assumption of a joint multivariate normal distribution for CAST scores and the 3 ASD diagnostic categories (unaffected, broad-spectrum disorder, and ASD) allowed the estimation of correlations within and across MZ/DZ twin pairs.”

  • The authors state this as an assumption.

    MZ and DZ twins experience equivalent environments.

    “twin study methods assume that the environments of MZ and DZ53 twins are equal”

  • The authors state this as an assumption.

    Twins do not have an unusually elevated risk for the condition being studied.

    “and that twins are not at especially high risk for the disorder under investigation.”

  • The authors state this as an assumption.

    No gene-environment interactions or correlations exist.

    “genetic modeling assumes that no gene-environment interactions or correlations exist”
5 of 5

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Autism is strongly influenced by the genome, with heritability estimates generally centering around 50% to 55%.

    “It is known that autism is strongly influenced by the genome-in contrast to earlier speculation, ranges of heritability estimates generally center ~50 or 55%”

    From The Role of the Immune System in Autism Spectrum Disorder (2017) · cites this paper as Colvert et al, 2015

  • Strong concordance of ASD in monozygotic twins compared to dizygotic twins reveals an ASD heritability rate of about 50%.

    “The strong concordance of ASD in monozygotic twins compared to dizygotic twins reveals an ASD heritability rate of about 50% (80, 81).”

    From Emerging Roles for the Gut Microbiome in Autism Spectrum Disorder (2017) · cites this paper as [81]

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Authors
Colvert, E., Tick, B., McEwen, F., Stewart, C., Curran, S. R., Woodhouse, E., Gillan, N., Hallett, V., Lietz, S., Garnett, T., Ronald, A., Plomin, R., Rijsdijk, F., Happé, F., & Bolton, P.
Affiliations
  • King's College London (GB)
  • National Health Service (GB)
  • Brighton and Sussex Medical School (GB)
  • University College London (GB)
  • University of London (GB)
  • MRC Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London, London, England
Corresponding author
Tick, Beata
ORCID
Venue
JAMA Psychiatry
Publisher
American Medical Association (AMA)
Published
2015-05-01
Volume
72
Issue
5
Pages
415
ISSN
2168-622X (ISSN-L)
DOI
10.1001/jamapsychiatry.2014.3028
PMC
PMC4724890
OpenAlex
W2153438724
Cited by
560
References
59
Citations by year
2026: 90 · 2025: 28 · 2024: 25 · 2023: 37 · 2022: 42 · 2021: 53 · 2020: 62 · 2019: 82 · 2018: 42 · 2017: 33 · 2016: 42 · 2015: 21 · 2014: 1
FWCI
27.62
Type
journal article
Language
en
Open access
Locations
  • JAMA Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • BIROn (Birkbeck, University of London) (submittedVersion)
  • Research Portal (King's College London) (submittedVersion, other-oa)
Funders
  • Autism Speaks
  • National Institute for Health and Care Research (NF-SI-0510-10268)
  • Medical Research Council (G0500870, G0901245, G0500079, MR/J500380/1)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords
autism spectrum disorder, heritability, genetic susceptibility, monozygotic twins, dizygotic twins, additive genetic effects, shared environmental effects, autistic traits, Twins Early Development Study
MeSH terms
Adolescent, Child, Child Development Disorders, Pervasive, Diseases in Twins, England, Environment, Female, Humans, Male, Models, Genetic, Phenotype, Twins, Dizygotic, Twins, Monozygotic, Wales, Genetic Predisposition to Disease

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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

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