CohortAutism research : official journal of the International Society for Autism Research2021

Expression Changes in Epigenetic Gene Pathways Associated With One-Carbon Nutritional Metabolites in Maternal Blood From Pregnancies Resulting in Autism and Non-Typical Neurodevelopment.

Yihui Zhu, Charles E Mordaunt, Blythe P Durbin-Johnson and 10 others

PMID 33159718

WHAT IT FOUND

Maternal blood gene expression during pregnancy differed in mothers of children who later developed autism or non-typical neurodevelopment.

These differences involved immune and epigenetic pathways, but no single gene or nutrient level was a strong enough predictor to serve as a clinical test.

Key findings

01Six transcripts in four genes (TGR-AS1, SQSTM1, HLA-C, RFESD) were associated with child outcomes (ASD, Non-TD, TD) with genome-wide significance.

02Maternal one-carbon metabolites (like folic acid) were not significantly associated with the child's clinical outcome, but were associated with gene expression modules.

03Gene expression changes associated with autism and non-typical outcomes were enriched for immune response pathways, specifically interferon-gamma signaling.

STILL TO COME

How it was doneWhat they found

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What it does not show

The study was underpowered to detect small differences in individual gene expression, meaning many potential biological signals may have been missed. Maternal blood contains many different cell types, and while the researchers adjusted for this, it complicates the interpretation of gene expression changes. Nutrient measurements were not available for all samples, reducing the ability to link specific dietary factors to gene expression changes. The study looked at associations, not causation; it cannot prove that these gene changes caused the developmental outcomes.

Declared interests

The authors declared no conflicts of interest. The study was funded by the NIH (NICHD, NIEHS).

The easy way to misread this

Do not interpret the identified gene pathways or nutrient associations as evidence that specific supplements or immune-targeted therapies will prevent or treat autism. The study describes biological mechanisms in a high-risk cohort and does not test any clinical interventions.

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The study

Participants
300 maternal blood samples (children: 67 ASD, 79 Non-TD, 154 TD)
Certainty of evidence
Low

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    Yihui Zhu, Charles E Mordaunt, Blythe P Durbin-Johnson, et al. Expression Changes in Epigenetic Gene Pathways Associated With One-Carbon Nutritional Metabolites in Maternal Blood From Pregnancies Resulting in Autism and Non-Typical Neurodevelopment. Autism research : official journal of the International Society for Autism Research. 2021.

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