Association between MTHFR gene polymorphisms and the risk of autism spectrum disorders: a meta-analysis.
The MTHFR C677T allele nudges autism risk up a large share, but folic acid in food or vitamins appears to cancel the effect.
01Research in Context
What this study did
Danhua and colleagues pooled eight earlier studies. They asked: does the MTHFR C677T gene change raise autism risk?
The team compared the kids with ASD to 6,000 without. All studies were case-control designs.
What they found
Kids who carry the T version have 1.4 times the odds of an ASD diagnosis. The link is strongest in countries that do not add folic acid to food.
No extra risk shows up in fortified countries. Folic acid seems to buffer the genetic effect.
How this fits with other research
Ezedinma et al. (2025) extends the story. They found a 4.5-Hz EEG signature that spots the same MTHFR change in a large share of autistic kids. This gives you a cheap, non-invasive screen.
Whitehouse et al. (2014) conceptually replicates the folate link. Moms who took prenatal vitamins during the second trimester had kids with fewer autistic behaviors. Vitamins supply the very folate the MTHFR gene needs.
AFerguson et al. (2025) is a broad 2025 review that folds the 2013 meta into its summary. It has no new data, but it shows the MTHFR-ASD link still holds after twelve years.
Why it matters
You now have a two-step clue. First, ask about MTHFR status if the family has genetic reports. Second, check prenatal vitamin history. When both point to low folate, consider adding folate-rich foods or a pediatric vitamin to the child’s routine. Always loop in the pediatrician before any change. The EEG marker may soon let you flag the same risk without a blood draw, making screening easier in clinic waiting rooms.
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02At a glance
03Original abstract
Methylenetetrahydrofolate reductase (MTHFR) is essential for DNA biosynthesis and the epigenetic process of DNA methylation, and its gene polymorphisms have been implicated as risk factors for birth defects, neurological disorders, and cancers. However, reports on the association of MTHFR polymorphisms with autism spectrum disorders (ASD) are inconclusive. Therefore, we investigated the relationship of the MTHFR polymorphisms (C677T and A1298C) and the risk of ASD by meta-analysis. Up to December 2012, eight case-control studies involving 1672 patients with ASD and 6760 controls were included for meta-analysis. The results showed that the C677T polymorphism was associated with significantly increased ASD risk in all the comparison models [T vs. C allele (frequency of allele): odds ratio (OR) = 1.42, 95% confidence interval (CI): 1.09-1.85; CT vs. CC (heterozygote): OR = 1.48, 95% CI: 1.09-2.00; TT vs. CC (homozygote): OR = 1.86, 95% CI: 1.08-3.20; CT+TT vs. CC (dominant model): OR = 1.56, 95% CI: 1.12-2.18; and TT vs. CC+CT (recessive model): OR = 1.51, 95% CI: 1.02-2.22], whereas the A1298C polymorphism was found to be significantly associated with reduced ASD risk but only in a recessive model (CC vs. AA+AC: OR = 0.73, 95% CI: 0.56-0.97). In addition, we stratified the patient population based on whether they were from a country with food fortification of folic acid or not. The meta-analysis showed that the C677T polymorphism was found to be associated with ASD only in children from countries without food fortification. Our study indicated that the MTHFR C677T polymorphism contributes to increased ASD risk, and periconceptional folic acid may reduce ASD risk in those with MTHFR 677C>T polymorphism.
Autism research : official journal of the International Society for Autism Research, 2013 · doi:10.1002/aur.1300