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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Acknowledgments
We extend our sincere appreciation to our research subjects and their extended family members for their enthusiastic support of this study and acknowledge the resources provided by the AGRE (Autism Genetics Resource Exchange) consortium and the participating AGRE families. AGRE is a program of Cure Autism Now and supported, in part, by grant MH64547 from the NIMH to Daniel H. Geschwind (PI). This work was supported by an OMHF grant (JJAH principal investigator) and a CIHR Interdisciplinary Health Research Team grant (RT-43820) to the Autism Spectrum Disorders Canadian-American Research Consortium (ASD-CARC: www.autismresearch.ca) (JJAH, principal investigator); MESL sincerely appreciates the support provided by a Michael Smith Foundation for Health Research Career Investigator (Scholar) Award (2005–2010); and we appreciate the support of the New York State Office for People with Developmental Disabilities (OPWDD).
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Liu, X., Solehdin, F., Cohen, I.L. et al. Population- and Family-Based Studies Associate the MTHFR Gene with Idiopathic Autism in Simplex Families. J Autism Dev Disord 41, 938–944 (2011). https://doi.org/10.1007/s10803-010-1120-x
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DOI: https://doi.org/10.1007/s10803-010-1120-x