Inherited risk for autism through maternal and paternal lineage
Open accessAbstract
BACKGROUND: Autism spectrum disorder (ASD) is highly familial, with a positively skewed male-to-female ratio that is purported to arise from the so-called female protective effect. A serious implication of a female protective effect is that familial ASD liability would be expected to aggregate asymptomatically in sisters of affected probands, who would incur elevated rates of ASD among their offspring. Currently, there exist no data on second-generation recurrence rates among families affected by ASD. METHODS: We analyzed data from the Swedish National Patient Register and the Multi-Generation Register for a cohort of children born between 2003 and 2012. ASD was ascertained in both the child and parental generations. RESULTS: Among 847,732 children, 13,103 (1.55%) children in the cohort were diagnosed with ASD. Among their maternal/paternal aunts and uncles, 1744 (0.24%) and 1374 (0.18%) were diagnosed with ASD, respectively. Offspring of mothers with a sibling(s) diagnosed with ASD had higher rates of ASD than the general population (relative risk, 3.05; 95% confidence interval, 2.52-3.64), but not more than would be predicted for second-degree relatives within a generation, and only slightly more than was observed for fathers with siblings with ASD (relative risk, 2.08; 95% confidence interval, 1.53-2.67). Models adjusting for temporal trends and for psychiatric history in the parental generation did not alter the results. CONCLUSIONS: These findings establish a robust general estimate of ASD transmission risk for siblings of individuals affected by ASD, the first ever reported. Our findings do not suggest female protective factors as the principal mechanism underlying the male sex bias in ASD.
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Several previous studies have considered the FPE through familial recurrence, with inconsistent results.
“Several previous studies have considered the FPE through familial recurrence, with inconsistent results.21, 22, 23, 24”
From The female protective effect against autism spectrum disorder (2022) · cites this paper as [22]
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- Authors
- Bai, D., Marrus, N., Yip, B. H. K., Reichenberg, A., Constantino, J. N., & Sandin, S.
- Affiliations
- Chinese University of Hong Kong (HK)
- Washington University in St. Louis (US)
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Sandin, Sven
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2020-09
- Volume
- 88
- Issue
- 6
- Pages
- 480-487
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC7483301
- OpenAlex
- W3014296189
- Cited by
- 45
- References
- 39
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 10 · 2023: 7 · 2022: 12 · 2021: 7 · 2020: 3
- FWCI
- 3.90
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Biological Psychiatry (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion, cc-by-nc-nd)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD087011)
- European Commission (PM04-2016)
- National Institute of Mental Health (K08MH112891)
- Autism Science Foundation
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Social Sciences › Psychology › Clinical Psychology › Family and Disability Support Research
- Keywords
- autism spectrum disorder, familial risk, heritability, recurrence risk
- MeSH terms
- Autism Spectrum Disorder, Autistic Disorder, Child, Fathers, Female, Humans, Male, Risk Factors, Sweden, Siblings
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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