Dataset Information

Potential role for immune-related genes in autism spectrum disorders: Evidence from genome-wide association meta-analysis of autistic traits.

ABSTRACT:

Lay abstract

Autism spectrum disorders are complex, with a strong genetic basis. Genetic research in autism spectrum disorders is limited by the fact that these disorders are largely heterogeneous so that patients are variable in their clinical presentations. To address this limitation, we investigated the genetics of individual dimensions of the autism spectrum disorder phenotypes, or autistic-like traits. These autistic-like traits are continuous variations in autistic behaviours that occur in the general population. Therefore, we meta-analysed data from four different population cohorts in which autistic-like traits were measured. We performed a set of genetic analyses to identify common variants for autistic-like traits, understand how these variants related to autism spectrum disorders, and how they contribute to neurobiological processes. Our results showed genetic associations with specific autistic-like traits and a link to the immune system. We offer an example of the potential to use a dimensional approach when dealing with heterogeneous, complex disorder like autism spectrum disorder. Decomposing the complex autism spectrum disorder phenotype in its core features can inform on the specific biology of these features which is likely to account to clinical variability in patients.

SUBMITTER: Arenella M

PROVIDER: S-EPMC8814945 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Potential role for immune-related genes in autism spectrum disorders: Evidence from genome-wide association meta-analysis of autistic traits.

Arenella Martina M Cadby Gemma G De Witte Ward W Jones Rachel M RM Whitehouse Andrew Jo AJ Moses Eric K EK Fornito Alex A Bellgrove Mark A MA Hawi Ziarih Z Johnson Beth B Tiego Jeggan J Buitelaar Jan K JK Kiemeney Lambertus A LA Poelmans Geert G Bralten Janita J

Autism : the international journal of research and practice 20210804 2

<h4>Lay abstract</h4>Autism spectrum disorders are complex, with a strong genetic basis. Genetic research in autism spectrum disorders is limited by the fact that these disorders are largely heterogeneous so that patients are variable in their clinical presentations. To address this limitation, we investigated the genetics of individual dimensions of the autism spectrum disorder phenotypes, or autistic-like traits. These autistic-like traits are continuous variations in autistic behaviours that ...[more]

PMID: 34344231

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Project description:ImportanceThe frequency with which autism spectrum disorders (ASDs) are diagnosed has shown a marked increase in recent years. One suggestion is that this is partly because of secular changes in the environment, yet to our knowledge this hypothesis lacks evidence.ObjectiveTo assess whether the relative importance of genetic and environmental associations with ASD and autistic traits has changed over a 16-year and 26-year period.Design, setting, and participantsA twin design was used to assess whether the heritability of ASD and autistic traits has changed over time. Data from 2 nationwide Swedish twin cohorts was used: the Swedish Twin Registry (STR; participants born between January 1982 and December 2008) and the Child and Adolescent Twin Study in Sweden (CATSS; participants born between January 1992 and December 2008). Autism spectrum disorder diagnoses were identified for twins in the STR, with follow-up to 2013. Questionnaires assigned screening diagnoses of ASD to CATSS participants and assessed autistic traits. Analyses were performed from September 1, 2018, to March 31, 2019.ExposuresEach sample was divided into several birth cohorts covering 1982 to 1991 (for the STR only), 1992-1995, 1996-1999, 2000-2003, and 2004-2008.OutcomesWe assessed whether the genetric and environment variance underlying autistic traits changed across birth cohorts and examined whether the relative contribution of genetics and environment to liability for autism changed across birth cohorts.ResultsData were available for 22 678 twin pairs (5922 female same-sex pairs [26.1%], 5563 male same-sex pairs [24.5%], and 11193 opposite-sex pairs [49.4%]) in the STR and 15 280 pairs (4880 female same-sex pairs [31.9%], 5092 male same-sex pairs [33.3%], and 5308 opposite-sex pairs [34.7%]) in CATSS. The heritability of ASD diagnoses in the STR ranged from 0.88 (95% CI, 0.74-0.96) to 0.97 (95% CI, 0.89-0.99). The heritability of screening diagnoses in CATSS varied from 0.75 (95% CI, 0.58-0.87) to 0.93 (95% CI, 0.84-0.98). Autistic traits showed a modest variance increase over time that was associated with increases in genetic and environmental variance, with the total variance increasing from 0.95 (95% CI, 0.92-0.98) to 1.17 (95% CI, 1.13-1.21) over time.Conclusions and relevanceWeak evidence was found for changes in the genetic and environmental factors underlying ASD and autistic traits over time. Genetic factors played a consistently larger role than environmental factors. Environmental factors are thus unlikely to explain the increase in the prevalence of ASD.

Project description:BackgroundA considerable amount of research has discussed whether autism and psychiatric/neurodevelopmental conditions in general are best described categorically or dimensionally. In recent years, finite mixture models have been increasingly applied to mixed populations of autistic and non-autistic individuals to answer this question. However, the use of such methods with mixed populations may not be appropriate for two reasons: First, subgroups within mixed populations are often skewed and thus violate mixture models assumptions, which are based on weighted sum of Gaussian distributions. Second, these analyses have, to our knowledge, been solely applied to enriched samples, where the prevalence of the clinical condition within the study sample far exceeds epidemiological estimates.MethodWe employed a dual Weibull mixture model to examine the distribution of the Autism Spectrum Quotient scores of a mixed sample of autistic and non-autistic adults (N = 4717; autism = 811), as well as of a derived sample (from the enriched sample; N = 3973; autism = 67) that reflects the current prevalence of autism within the general population.ResultsIn a mixed autistic and non-autistic population, our model provided a better description of the underlying structure of autistic traits than traditional finite Gaussian mixture models and performed well when applied to a sample that reflected the prevalence of autism in the general population. The model yielded results, which are consistent with predictions of current theories advocating for the co-existence of a mixed categorical and dimensional architecture within the autism spectrum.ConclusionThe results provide insight into the continuum nature of the distribution of autistic traits, support the complementary role of both categorical and dimensional approaches to autism spectrum condition, and underscore the importance of analyzing samples that reflect the epidemiological prevalence of the condition. Owing to its flexibility to represent a wide variety of distributions, the Weibull distribution might be better suited for latent structure studies, within enriched and prevalence-true samples.

Project description:Altered trajectories of brain growth are often reported in Autism Spectrum Disorder (ASD), particularly during the first year of life. However, less is known about prenatal head growth trajectories, and no study has examined the relation with postnatal autistic symptom severity. The current study prospectively examined the association between fetal head growth and the spectrum of autistic symptom severity in two large population-based cohorts, including a sample of individuals with clinically diagnosed ASD. This study included 3,820 children from two longitudinal prenatal cohorts in The Netherlands and Australia, comprising 60 individuals with a confirmed diagnosis of ASD. Latent growth curve models were used to examine the relationship between fetal head circumference measured at three different time points and autistic traits measured in postnatal life using either the Social Responsiveness Scale or the Autism-Spectrum Quotient. While lower initial prenatal HC was weakly associated with increasing autistic traits in the Dutch cohort, this relationship was not observed in the Australian cohort, nor when the two cohorts were analysed together. No differences in prenatal head growth were found between individuals with ASD and controls. This large population-based study identified no consistent association across two cohorts between prenatal head growth and postnatal autistic traits. Our mixed findings suggest that further research in this area is needed. Autism Res 2018, 11: 602-612. © 2018 The Authors Autism Research published by International Society for Autism Research and Wiley Periodicals, Inc.Lay summaryIt is not known whether different patterns of postnatal brain growth in Autism Spectrum Disorder (ASD) also occurs prenatally. We examined fetal head growth and autistic symptoms in two large groups from The Netherlands and Australia. Lower initial prenatal head circumference was associated with autistic traits in the Dutch, but not the Australian, group. No differences in head growth were found in individuals with ASD and controls when the data was combined. Our mixed findings suggest that more research in this area is needed.

Dataset Information

Potential role for immune-related genes in autism spectrum disorders: Evidence from genome-wide association meta-analysis of autistic traits.

Lay abstract

Publications

Potential role for immune-related genes in autism spectrum disorders: Evidence from genome-wide association meta-analysis of autistic traits.

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