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Integrated genetic and methylomic analyses identify shared biology between autism and autistic traits.

ABSTRACT: Previous studies have identified differences in DNA methylation in autistic individuals compared to neurotypical individuals. Yet, it is unclear if this extends to autistic traits-subclinical manifestation of autism features in the general population. Here, we investigate the association between DNA methylation at birth (cord blood), and scores on the Social and Communication Disorders Checklist (SCDC), a measure of autistic traits, in 701 8-year-olds, by conducting a methylome-wide association study (MWAS). We did not identify significant CpGs associated with SCDC. The most significant CpG site was cg14379490, on chromosome 9 (MWAS beta?=?-?1.78?±?0.35, p value?=?5.34?×?10 -7 ). Using methylation data for autism in peripheral tissues, we did not identify a significant concordance in effect direction of CpGs with p value ?0.5). In contrast, using methylation data for autism from post-mortem brain tissues, we identify a significant concordance in effect direction of CpGs with a p value

SUBMITTER: Massrali A

PROVIDER: S-EPMC6637466 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Integrated genetic and methylomic analyses identify shared biology between autism and autistic traits.

Massrali Aicha A Brunel Helena H Hannon Eilis E Wong Chloe C Baron-Cohen Simon S Warrier Varun V

Molecular autism 20190717

Previous studies have identified differences in DNA methylation in autistic individuals compared to neurotypical individuals. Yet, it is unclear if this extends to autistic traits-subclinical manifestation of autism features in the general population. Here, we investigate the association between DNA methylation at birth (cord blood), and scores on the Social and Communication Disorders Checklist (SCDC), a measure of autistic traits, in 701 8-year-olds, by conducting a methylome-wide association ...[more]

PMID: 31346403

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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.

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Integrated genetic and methylomic analyses identify shared biology between autism and autistic traits.

Publications

Integrated genetic and methylomic analyses identify shared biology between autism and autistic traits.

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