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

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

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Autism spectrum disorder (ASD) is highly heritable, yet how its familial risk and heritability may vary by cognitive ability is not well understood. In this population‐based cohort study, we examined the familial risk and heritability of ASD with and without co‐occurring intellectual disability (ID). We estimated odds ratios and heritability of ASD with ID (ASD+ID) and ASD without ID (ASD?ID) using register‐based diagnosis data of 567,436 index persons born in 1984–2009 in Stockholm County, Sweden, and their parents, siblings, cousins, aunts, and uncles. The familial risk profile exhibited differences between ASD?ID and ASD+ID, most notably for index persons with affected parents. For example, for an index person who had at least one parent with ASD, the child's odds of ASD?ID and ASD+ID (95 confidence interval (CI)) increased by 16.2 (14.2–18.6) and 7.4 (5.5–10.0) folds, respectively. The more closely related a family member with ASD was, the greater the observed risk was of ASD in the index person, especially for ASD?ID. The broad‐sense heritability (95 CI) for ASD???ID and ASD+ID were 64.6 (46.0–100.0) and 33.4 (14.4–58.4), respectively. Familial risk and heritability of ASD may vary by intellectual ability, which implies that risk factors between these ASD phenotypes may differ. Our findings from the heritability analysis and familial risk analysis suggest that ASD?ID may have a greater genetic basis than ASD+ID, although this should be verified in future studies. Lay Summary Autism spectrum disorder (ASD) is highly heritable, yet how its familial risk and heritability may vary by cognitive ability is not well‐understood. In a population‐based cohort study on families of 567,436 index persons using Swedish registers data, we found that the familial risk profile differed between ASD with and without intellectual disability. Our findings from the heritability analysis and familial risk analysis suggest that ASD?ID may have a greater genetic basis than ASD+ID, although this should be verified in future studies.

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