CohortAutism research : official journal of the International Society for Autism Research2020

The Familial Risk of Autism Spectrum Disorder with and without Intellectual Disability.

Sherlly Xie, Håkan Karlsson, Christina Dalman and 8 others

PMID 33103358

WHAT IT FOUND

Family history of autism spectrum disorder was more strongly linked to autism without intellectual disability than to autism with it, especially when the affected relative was a parent.

Key findings

01Family history of autism spectrum disorder was associated with higher odds of autism without intellectual disability and autism with intellectual disability, and odds were higher when the affected relative was a closer relative.

02Having an affected mother was associated with a 19.6-fold increase in odds of autism without intellectual disability and a 10.8-fold increase in odds of autism with intellectual disability; affected fathers also showed a larger association for autism without intellectual disability.

03The model attributed 64.6% of the liability of autism without intellectual disability to the total genetic component and 33.4% of the liability of autism with intellectual disability to the total genetic component, but the authors state these estimates are imprecise.

STILL TO COME

How it was doneWhat they found

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What it does not show

This is an observational register study, not a trial, so it cannot show that any treatment changes autism or intellectual disability outcomes. The heritability estimates are imprecise, especially for autism without intellectual disability, where the confidence interval ranged from 46.0% to 100.0%. Heritability describes population variation in liability, not how much of an individual's condition is caused by genes, and the model did not account for gene-environment interactions. ASD diagnosis codes became available in 1987, so familial risk estimates for earlier born individuals may be less accurate. The sample was restricted to singletons, so findings may not generalize to multiple births. Relatives of affected individuals may have been more readily diagnosed because of detection bias. The study did not examine mediation by family psychiatric history, and residual confounding or underreporting of intellectual disability may remain. The study did not stratify by time period, so cohort effects may have influenced results.

Declared interests

The authors declared no conflicts of interest.

The easy way to misread this

Do not read the higher familial risk and model-based genetic contribution for autism without intellectual disability as proof that autism with intellectual disability is less familial or as a way to predict an individual child's cause. The study is observational, the confidence intervals are wide, and heritability describes population variation, not an individual's condition.

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The study

Participants
567,436 index persons; 8,354 had autism without intellectual disability and 2,566 had autism with intellectual disability
Certainty of evidence
Low

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    Cite

    Sherlly Xie, Håkan Karlsson, Christina Dalman, et al. The Familial Risk of Autism Spectrum Disorder with and without Intellectual Disability. Autism research : official journal of the International Society for Autism Research. 2020.

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