Population- and Family-Based Studies Associate the MTHFR Gene with Idiopathic Autism in Simplex Families
Abstract
Two methylenetetrahydrofolate reductase gene (MTHFR) functional polymorphisms were studied in 205 North American simplex (SPX) and 307 multiplex (MPX) families having one or more children with an autism spectrum disorder. Case-control comparisons revealed a significantly higher frequency of the low-activity 677T allele, higher prevalence of the 677TT genotype and higher frequencies of the 677T-1298A haplotype and double homozygous 677TT/1298AA genotype in affected individuals relative to controls. Family-based association testing demonstrated significant preferential transmission of the 677T and 1298A alleles and the 677T-1298A haplotype to affected offspring. The results were not replicated in MPX families. The results associate the MTHFR gene with autism in SPX families only, suggesting that reduced MTHFR activity is a risk factor for autism in these families.
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Several studies have reported an association of ASD with single-nucleotide polymorphisms in a gene which is directly involved in methylation.
“several studies have reported an association of ASD with single-nucleotide polymorphisms in a gene which is directly involved in methylation”
From Autism risk factors: genes, environment, and gene-environment interactions (2012) · cites this paper as [75]
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Jensen, R. (2013) · OA Autism · doi:10.13172/2052-7810-1-1-578
Frye, R. E., & Rossignol, D. A. (2014) · WORLD SCIENTIFIC eBooks · doi:10.1142/9789814602167_0022
Examining the Influence and Role of Pharmacogenetics among Children with Autism Spectrum Disorder
Shaker, N. (2017) · TopSCHOLAR (Western Kentucky University)
Geng, L. Y., Ji, C. W., Chen, C., & Huang, P. (2021) · Indian Journal of Pharmaceutical Sciences · doi:10.36468/pharmaceutical-sciences.spl.286
- Authors
- Liu, X., Solehdin, F., Cohen, I. L., Gonzalez, M. G., Jenkins, E. C., Lewis, M. E. S., & Holden, J. J. A.
- Affiliations
- Queen's University (CA)
- University of British Columbia (CA)
- Corresponding author
- Holden, Jeanette J. A.
- Venue
- Journal of Autism and Developmental Disorders
- Published
- 2010-11-12
- Volume
- 41
- Issue
- 7
- Pages
- 938-944
- ISSN
- 0162-3257 (ISSN-L)
- 1573-3432
- OpenAlex
- W2029074253
- Cited by
- 62
- References
- 49
- Citations by year
- 2025: 3 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 6 · 2019: 6 · 2018: 6 · 2017: 4 · 2016: 5 · 2015: 3 · 2014: 7 · 2013: 7 · 2012: 4
- FWCI
- 2.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Autism and Developmental Disorders (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Office for People With Developmental Disabilities
- Michael Smith Health Research BC
- Canadian Institutes of Health Research (43820_1)
- National Institute of Mental Health (MH 64547, R01MH064547)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
- Keywords
- MTHFR, methylenetetrahydrofolate reductase, idiopathic autism, autism spectrum disorder, simplex families, multiplex families, genetic association, folate metabolism, genetic risk
- MeSH terms
- Alleles, Autistic Disorder, Child, Female, Gene Frequency, Genotype, Haplotypes, Humans, Male, Polymorphism, Single Nucleotide, Methylenetetrahydrofolate Reductase (NADPH2), Genetic Association Studies
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