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Related Experiment Video

Updated: Jul 9, 2025

Generating a Reproducible Model of Mid-Gestational Maternal Immune Activation using PolyI:C to Study Susceptibility and Resilience in Offspring
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Genetic relationship between the immune system and autism.

Martina Arenella1,2,3, Giuseppe Fanelli2,3,4, Lambertus A Kiemeney5

  • 1Department of Forensic and Neurodevelopmental Science, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.

Brain, Behavior, & Immunity - Health
|November 29, 2023
PubMed
Summary

Genetic links between autism spectrum disorder (ASD) and immune system conditions reveal that some immune factors increase ASD risk, while others may offer resilience. These connections are specific to certain genetic areas and autistic traits like rigidity.

Keywords:
AutismAutistic traitsGWASImmunePolygenic risk scores

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Area of Science:

  • Immunology
  • Genetics
  • Neurodevelopmental Disorders

Background:

  • Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with a significant genetic component.
  • Emerging evidence suggests immune dysregulation plays a role in ASD pathophysiology, but specific genetic links remain unclear.

Purpose of the Study:

  • To investigate the genetic correlation between ASD and various immune conditions and markers.
  • To determine if immune-related genetic factors are associated with specific autistic-like traits.

Main Methods:

  • Genome-wide association study (GWAS) summary statistics were used to estimate genetic correlations between ASD and 11 immune phenotypes.
  • Polygenic scores (PGS) for immune phenotypes were calculated in a population sample and associated with autistic-like traits.
  • Sex-stratified analyses were conducted.

Main Results:

  • Genome-wide, ASD showed positive genetic correlation with allergic diseases (ALG) and negative correlation with lymphocyte count, rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE).
  • Local genetic analysis revealed correlations between ASD and RA, C-reactive protein, and granulocyte/lymphocyte counts.
  • Higher genetic liability for SLE, RA, ALG, and lymphocyte levels was associated with increased autistic traits, particularly rigidity and childhood behavior.

Conclusions:

  • A significant genetic relationship exists between ASD and immunity, varying by immune phenotype.
  • Certain immune genetic factors may increase ASD risk, while others might confer resilience.
  • The genetic links are locus-specific and associated with particular dimensions of autism, such as rigidity.