Journal of Autism and Developmental Disorders

, Volume 41, Issue 7, pp 938–944

Population- and Family-Based Studies Associate the MTHFR Gene with Idiopathic Autism in Simplex Families

  • Xudong Liu
  • Fatima Solehdin
  • Ira L. Cohen
  • Maripaz G. Gonzalez
  • Edmund C. Jenkins
  • M. E. Suzanne Lewis
  • Jeanette J. A. Holden
Original Paper


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.


Autism spectrum disorders (ASDs) Gene association Methylenetetrahydrofolate reductase (MTHFRFunctional polymorphism Epigenetics Methylation 


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Xudong Liu
    • 1
    • 6
  • Fatima Solehdin
    • 2
    • 6
  • Ira L. Cohen
    • 4
    • 6
  • Maripaz G. Gonzalez
    • 4
    • 6
  • Edmund C. Jenkins
    • 5
    • 6
  • M. E. Suzanne Lewis
    • 2
    • 3
    • 6
  • Jeanette J. A. Holden
    • 1
    • 6
    • 7
  1. 1.Department of Psychiatry & PhysiologyQueen’s University, Autism Research Program, Ongwanada Resource CentreKingstonCanada
  2. 2.Department of Medical GeneticsUniversity of British ColumbiaVancouverCanada
  3. 3.BC Child and Family Research InstituteVancouverCanada
  4. 4.Department of PsychologyNew York State Institute for Basic Research in Developmental DisabilitiesStaten IslandUSA
  5. 5.Department of Human GeneticsNew York State Institute for Basic Research in Developmental DisabilitiesStaten IslandUSA
  6. 6.The Autism Spectrum Disorders-Canadian American Research Consortium (ASD-CARC)KingstonCanada
  7. 7.

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