A Twin Study of Heritable and Shared Environmental Contributions to Autism

Frazier, Thomas; Thompson, Lee A.; Youngstrom, Eric A.; Law, Paul A.; Hardan, Antonio Y.; Eng, Charis; Morris, Nathan

doi:10.1007/s10803-014-2081-2

Cited by 102 publications

(82 citation statements)

References 84 publications

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“…ASDs are estimated to occur in 1/42 boys and 1/189 girls, and are among the most heritable common disorders[1]. Estimates of heritability for idiopathic ASDs range between 38% and 90%, and autism-related traits in the general population are similarly heritable[2–9]. An emerging body of evidence has identified a wide array of potential non-genetic risk factors[10,11].…”

Section: Introductionmentioning

confidence: 99%

Pleiotropic Mechanisms Indicated for Sex Differences in Autism

et al. 2016

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Sexual dimorphism in common disease is pervasive, including a dramatic male preponderance in autism spectrum disorders (ASDs). Potential genetic explanations include a liability threshold model requiring increased polymorphism risk in females, sex-limited X-chromosome contribution, gene-environment interaction driven by differences in hormonal milieu, risk influenced by genes sex-differentially expressed in early brain development, or contribution from general mechanisms of sexual dimorphism shared with secondary sex characteristics. Utilizing a large single nucleotide polymorphism (SNP) dataset, we identify distinct sex-specific genome-wide significant loci. We investigate genetic hypotheses and find no evidence for increased genetic risk load in females, but evidence for sex heterogeneity on the X chromosome, and contribution of sex-heterogeneous SNPs for anthropometric traits to ASD risk. Thus, our results support pleiotropy between secondary sex characteristic determination and ASDs, providing a biological basis for sex differences in ASDs and implicating non brain-limited mechanisms.

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Section: Introductionmentioning

confidence: 99%

Pleiotropic Mechanisms Indicated for Sex Differences in Autism

et al. 2016

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“…Researchers have also attempted to identify biological causes with wide‐reaching theories linked to genes, inflammation, metabolic differences and neuroimaging abnormalities . Genetic explorations, historically focused on twins and children with known genetic conditions with an increased risk of autism, have recently identified common variant genes linked to other conditions and potential epigenetic differences, which fit with gene–environment interaction theories currently being explored …”

Section: How Do We Move Towards Precision Medicine For Children Withmentioning

confidence: 99%

Autism: One or many spectrums?

Ure

Rose

Bernie

et al. 2018

J Paediatrics Child Health

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Our conceptualisation of autism spectrum disorder has changed over time, with recent classifications reflecting a heterogeneous clinical presentation now regularly encountered in routine general paediatric practice. As the prevalence of autism and associated demands for services have increased so has research into understanding the cause and trials aimed at providing best care and intervention. However, the heterogeneity of autism has meant that no single aetiology can account for all differences in presentation, and not all children benefit from broad‐based interventions. Now is the time to rethink how best to understand individual differences in order to focus research efforts and take steps towards more sophisticated strategies that go beyond the behaviours we look for when making an autism diagnosis. We suggest adopting a dimensional approach to autism assessment, with the consideration of eight spectrums of abilities, ways of thinking and behaviour. This eight‐spectrum approach will assist clinicians to consider each individual's strengths and needs and personalise interventions and support accordingly. Profiling individual skills across these dimensions may also provide researchers with a greater capacity to link causal pathways with specific phenotypes, which is needed to develop precision medicine for autism.

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“…Although there has been considerable debate in etiology of ASD, the genetic basis of this disorder is supported by several twin studies (Rosenberg et al, 2009;Frazier et al, 2014). Much attention has been focused on a relationship between ASD and a transcriptional gene, forkhead box P2 (FOXP2), which is closely related to language ability (Bowers and Konopka, 2012).…”

Section: Asd and Neuroinflammationmentioning

confidence: 99%

Involvement of Neuroinflammation during Brain Development in Social Cognitive Deficits in Autism Spectrum Disorder and Schizophrenia

Nakagawa¹,

Chiba²

2016

Journal of Pharmacology and Experimental Therapeutics

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Development of social cognition, a unique and high-order function, depends on brain maturation from childhood to adulthood in humans. Autism spectrum disorder (ASD) and schizophrenia have similar social cognitive deficits, although age of onset in each disorder is different. Pathogenesis of these disorders is complex and contains several features, including genetic risk factors, environmental risk factors, and sites of abnormalities in the brain. Although several hypotheses have been postulated, they seem to be insufficient to explain how brain alterations associated with symptoms in these disorders develop at distinct developmental stages. Development of ASD appears to be related to cerebellar dysfunction and subsequent thalamic hyperactivation in early childhood. By contrast, schizophrenia seems to be triggered by thalamic hyperactivation in late adolescence, whereas hippocampal aberration has been possibly initiated in childhood. One of the possible culprits is metal homeostasis disturbances that can induce dysfunction of blood-cerebrospinal fluid barrier. Thalamic hyperactivation is thought to be induced by microglia-mediated neuroinflammation and abnormalities of intracerebral environment. Consequently, it is likely that the thalamic hyperactivation triggers dysregulation of the dorsolateral prefrontal cortex for lower brain regions related to social cognition. In this review, we summarize the brain aberration in ASD and schizophrenia and provide a possible mechanism underlying social cognitive deficits in these disorders based on their distinct ages of onset.

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A Twin Study of Heritable and Shared Environmental Contributions to Autism

Cited by 102 publications

References 84 publications

Pleiotropic Mechanisms Indicated for Sex Differences in Autism

Pleiotropic Mechanisms Indicated for Sex Differences in Autism

Autism: One or many spectrums?

Involvement of Neuroinflammation during Brain Development in Social Cognitive Deficits in Autism Spectrum Disorder and Schizophrenia

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