The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
Genetic Heritability and Shared Environmental Factors Among Twin Pairs With Autism
Open accessAbstract
CONTEXT: Autism is considered the most heritable of neurodevelopmental disorders, mainly because of the large difference in concordance rates between monozygotic and dizygotic twins. OBJECTIVE: To provide rigorous quantitative estimates of genetic heritability of autism and the effects of shared environment. DESIGN, SETTING, AND PARTICIPANTS: Twin pairs with at least 1 twin with an autism spectrum disorder (ASD) born between 1987 and 2004 were identified through the California Department of Developmental Services. MAIN OUTCOME MEASURES: Structured diagnostic assessments (Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule) were completed on 192 twin pairs. Concordance rates were calculated and parametric models were fitted for 2 definitions, 1 narrow (strict autism) and 1 broad (ASD). RESULTS: For strict autism, probandwise concordance for male twins was 0.58 for 40 monozygotic pairs (95% confidence interval [CI], 0.42-0.74) and 0.21 for 31 dizygotic pairs (95% CI, 0.09-0.43); for female twins, the concordance was 0.60 for 7 monozygotic pairs (95% CI, 0.28-0.90) and 0.27 for 10 dizygotic pairs (95% CI, 0.09-0.69). For ASD, the probandwise concordance for male twins was 0.77 for 45 monozygotic pairs (95% CI, 0.65-0.86) and 0.31 for 45 dizygotic pairs (95% CI, 0.16-0.46); for female twins, the concordance was 0.50 for 9 monozygotic pairs (95% CI, 0.16-0.84) and 0.36 for 13 dizygotic pairs (95% CI, 0.11-0.60). A large proportion of the variance in liability can be explained by shared environmental factors (55%; 95% CI, 9%-81% for autism and 58%; 95% CI, 30%-80% for ASD) in addition to moderate genetic heritability (37%; 95% CI, 8%-84% for autism and 38%; 95% CI, 14%-67% for ASD). CONCLUSION: Susceptibility to ASD has moderate genetic heritability and a substantial shared twin environmental component.
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In the citing paper
“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 Hallmayer et al, 2011
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Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Two large, independent twin studies that examined the relative contributions of genetic heritability versus the shared environment similarly concluded that environmental factors were more predominant than genetic factors in determining autism risk [ 23 , 24 ].”
From DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders? (2016) · cites this paper as [23]
The cited source says what the claim attributes to it.
In the citing paper
“This is considerably lower than the 90% in earlier twin studies2–4 and closer to the 38% (14–67) reported in a recent California twin study7 but estimated with substantially higher precision”
From The Familial Risk of Autism (2014) · cites this paper as [7]
In the citing paper
“Several studies support currently the hypothesis that autism etiology is based on a polygenic and epistatic model.”
From Gene × Environment Interactions in Autism Spectrum Disorders: Role of Epigenetic Mechanisms (2014) · cites this paper as [9]
In the citing paper
“Hallmayer et al. (9) underline in their twin studies the involvement of both genetic and environmental factors in the development of ASD.”
From Gene × Environment Interactions in Autism Spectrum Disorders: Role of Epigenetic Mechanisms (2014) · cites this paper as [9]
In the citing paper
“In the Folstein and Rutter (29), Bailey et al. (30), and Hallmayer et al. (9) studies, concordance rates vary according to the diagnosis: the concordance rates are higher for the broader autism phenotype than for AD (full diagnostic criteria).”
From Gene × Environment Interactions in Autism Spectrum Disorders: Role of Epigenetic Mechanisms (2014) · cites this paper as [9]
In the citing paper
“The results of recent twin and family studies point toward a greater role for environmental contributions [29, 30]”
From The contribution of environmental exposure to the etiology of autism spectrum disorder (2019) · cites this paper as [30]
In the citing paper
“Environmental chemical exposures may act through pathophysiologies, including the direct disruption of cells and structures of the nervous system, endocrine hormone- or immune system-mediated impacts, epigenetic changes, and more (Table 1).”
From Environmental Chemical Exposures and Autism Spectrum Disorders: A Review of the Epidemiological Evidence (2014) · cites this paper as [7]
In the citing paper
“Secondly, genetics strongly contributes to the pathogenesis of AD, but many patients reveal no obviously pathogenic mutations or copy number variants, and initial heritability estimates as high as >90% [234] have been challenged by more recent twin studies [235].”
From Consensus Paper: Pathological Role of the Cerebellum in Autism (2012) · cites this paper as [235]
In the citing paper
“With one notable exception (Hallmayer et al., 2011), heritability estimates range from 52-90% (Chen et al., 2015; De Rubeis and Buxbaum, 2015a, b; Gaugler et al., 2014; Rosenberg et al., 2009; Sandin et al., 2014; Toro et al., 2010).”
From Unifying Views of Autism Spectrum Disorders: A Consideration of Autoregulatory Feedback Loops (2016) · cites this paper as Hallmayer et al., 2011
In the citing paper
“Two recent studies report somewhat higher rates of concordance in DZ twins (31%), suggesting, that the contribution of shared environmental factors could be greater than had been previously estimated (Hallmayer et al., 2011; Rosenberg et al., 2009).”
From CNVs: Harbingers of a Rare Variant Revolution in Psychiatric Genetics (2012) · cites this paper as Hallmayer et al., 2011
In the citing paper
“Heritability estimates based on studies of clinically ascertained twin samples (Bailey et al., 1995; Folstein and Rutter, 1977; Hallmayer et al., 2011; Steffenburg et al., 1989) vary widely, from 38% to 90%, but it is clear that genes play a major role in ASD.”
From CNVs: Harbingers of a Rare Variant Revolution in Psychiatric Genetics (2012) · cites this paper as Hallmayer et al., 2011
In the citing paper
“This model predicts that relatives of female probands should be at increased risk for ASD as compared with relatives of male probands, which is supported by a recent twin study [32].”
From Sex differences in autism spectrum disorders (2013) · cites this paper as [32]
In the citing paper
“Findings of ~60% concordance rate in monozygotic and ~25% concordance in dizygotic twin pairs”
From Sex differences in autism spectrum disorders (2013) · cites this paper as [32]
In the citing paper
“have recalibrated heritability estimates for ASD”
From Sex differences in autism spectrum disorders (2013) · cites this paper as [32]
In the citing paper
“and suggest that the gestational environment play a significant role in ASD susceptibility”
From Sex differences in autism spectrum disorders (2013) · cites this paper as [32]
In the citing paper
“A recent, large, population-based twin study of ASD concordance”
From Sex differences in autism spectrum disorders (2013) · cites this paper as [32]
In the citing paper
“recent reports have suggested that the environment may have a much larger role in causing ASD than had been initially proposed4,5.”
From Immune mediators in the brain and peripheral tissues in autism spectrum disorder (2015) · cites this paper as [4]
In the citing paper
“Early estimates of the heritability of ASD of around 90%14,15, and even recently revised estimates of between 38 and 54%, strongly suggest that genetic mutations are a major cause of ASD4,16.”
From Immune mediators in the brain and peripheral tissues in autism spectrum disorder (2015) · cites this paper as [4]
In the citing paper
“recent estimates suggest that between 50 and 60% of the risk for ASD is unaccounted for, which implies that environmental factors or gene–environment interactions contribute substantially to the risk for this disorder4,16.”
From Immune mediators in the brain and peripheral tissues in autism spectrum disorder (2015) · cites this paper as [4]
In the citing paper
“There is little evidence, however, that siblings of female probands exhibit a differential risk for the occurrence of categorical ASD [8, 21, 23–25].”
From Early sex differences are not autism-specific: A Baby Siblings Research Consortium (BSRC) study (2015) · cites this paper as [23]
In the citing paper
“The current lack of evidence for a proband sex effect on recurrence mirrors a recent population-based study [8] and reports on clinically diagnosed ASD cases [23, 24].”
From Early sex differences are not autism-specific: A Baby Siblings Research Consortium (BSRC) study (2015) · cites this paper as [23]
In the citing paper
“Heritable factors account for at least 50% of ASD risk with the remainder attributable to environmental factors acting alone or through interaction with genetics45.”
From Fetal and postnatal metal dysregulation in autism (2017) · cites this paper as [5]
In the citing paper
“evidence from twin studies suggest that while heritability is quite high,9 there is also a substantial environmental component for ASD susceptibility.10”
From Maternal immune activation dysregulation of the fetal brain transcriptome and relevance to the pathophysiology of autism spectrum disorder (2018) · cites this paper as [10]
In the citing paper
“Twin, family and population-based studies have shown ASD to be one of the most heritable of all psychiatric disorders, with heritability estimated at ~50% (see reviews in [119, 310]) and monozygotic twin concordance rates between 70 to 90% [1, 113, 139, 304, 344].”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [139]
In the citing paper
“These results are similar to those of recent population-based cohorts 4,9,10 as well as a recent metaanalysis of twin studies, 8 which estimated heritability in the range of 64% to 91%.”
From Association of Genetic and Environmental Factors With Autism in a 5-Country Cohort (2019) · cites this paper as [10]
In the citing paper
“and 3 population-based studies from Sweden recently estimated the heritability of ASD to be 83%, 9 80%, 4 and 66%. 10”
From Association of Genetic and Environmental Factors With Autism in a 5-Country Cohort (2019) · cites this paper as [10]
In the citing paper
“Another study recently challenged the high heritability model of autism, estimating the heritability of autism to be 55 %”
From Autism risk factors: genes, environment, and gene-environment interactions (2012) · cites this paper as [3]
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Metadata
- Authors
- Hallmayer, J.
- Affiliations
- Stanford Medicine (US)
- Corresponding author
- Hallmayer, Joachim
- ORCID
- Hallmayer, Joachim
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2011-11-01
- Volume
- 68
- Issue
- 11
- Pages
- 1095
- ISSN
- 0003-990X (ISSN-L)
- PMC
- PMC4440679
- OpenAlex
- W2167684047
- Cited by
- 1,970
- References
- 27
- Citations by year
- 2026: 44 · 2025: 55 · 2024: 96 · 2023: 96 · 2022: 116 · 2021: 123 · 2020: 194 · 2019: 118 · 2018: 120 · 2017: 131 · 2016: 176 · 2015: 168 · 2014: 185 · 2013: 171 · 2012: 150
- FWCI
- 85.95
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01MH067005)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- autism spectrum disorder, heritability, shared environment, monozygotic twins, dizygotic twins, twin concordance, liability, genetic and environmental effects, sex differences, twin pairs, neurodevelopmental disorders, heritability estimates, shared environmental factors
- MeSH terms
- Adolescent, Adult, California, Child, Child Development Disorders, Pervasive, Environment, Female, Humans, Male, Maternal Age, Models, Genetic, Sex Factors, Socioeconomic Factors, Twins, Monozygotic, Prevalence, Confidence Intervals, Risk Assessment, Patient Selection, Genetic Predisposition to Disease, Gene-Environment Interaction
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