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

In the paper

“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.”

In the paper

“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%]).”

In the paper

“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.”

In the paper

“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”

What the sources say

• Not checked yetcites [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

In the paper

“The phenotypic correlations were moderate to high (0.52-0.65), and genetic factors accounted for 77% to 100% of the covariance.”

In the paper

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

In the paper

“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%]).”

In the paper

“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.”

In the paper

“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”

What the sources say

• Not checked yetcites [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 yetcites [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 yetcites [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 yetcites [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 yetcites [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

In the paper

“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.”

What the sources say

• Not checked yetcites [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

In the paper

“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”

What the sources say

• Not checked yetcites [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 yetcites [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

In the paper

“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).”

What the sources say

• Not checked yetcites [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 yetcites [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

In the paper

“In addition, a large population study of extended families (approximately 2 million individuals)18 reported estimates of 50% for heritability and nonshared environmental factors.”

What the sources say

• Not checked yetcites [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

In the paper

“The ADI-R is a well-established diagnostic tool for the assessment of autism.36”

What the sources say

• Not checked yetcites [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

In the paper

“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).”

In the paper

“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).”

In the paper

“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.”

What the sources say

• Not checked yetcites [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 yetcites [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 yetcites [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 yetcites [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 yetcites [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 yetcites [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 yetcites [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 yetcites [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 yetcites [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

In the paper

“The ADOS is a well-validated, semistructured observational assessment designed to accompany the ADI-R in the diagnosis of ASD.37”

What the sources say

• Not checked yetcites [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

In the paper

“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”

What the sources say

• Not checked yetcites [28] Williams J Scott F Stott C The CAST (Childhood Asperger Syndrome Test): test accuracy Autism 2005 9 1 45 68 15618262

In the paper

“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.”

In the paper

“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.”

What the sources say

• Not checked yetcites [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

In the paper

“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).”

What the sources say

• Not checked yetcites [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

In the paper

“At stage 2, 62.1% of the 235 eligible families underwent diagnostic evaluations.”

In the paper

“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.”

What the sources say

• Not checked yetcites [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 yetcites [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

In the paper

“Among the group with high CAST scores or suspected ASD, 36.4% were female compared with 16.6% of the final sample.”

In the paper

“In comparison, 1 recent twin study did not confirm significant shared environmental effects and reported heritability of 95%.17”

What the sources say

• Not checked yetcites [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

In the paper

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

In the paper

“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).”

In the paper

“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.”

In the paper

“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.”

In the paper

“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.”

In the paper

“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).”

In the paper

“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.”

In the paper

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

In the paper

“Heritability estimates are also population specific and depend on the dynamic interaction with the current environment.”

In the paper

“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.”

What the sources say

• Not checked yetcites [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