A mitochondrial bioenergetic hypothesis for autism spectrum disorder (570.3)

We are testing the hypothesis that a significant proportion of the risk for developing Autism Spectrum Disorder (ASD) is the result of inheriting partial defects in genes for mitochondrial bioenergetics. To test our hypothesis, first we determined if ancient human mtDNA variation is associated with ASD risk. To accomplish this, we used two independently generated and genotyped cohorts, the Autism Genetic Resource Exchange (AGRE) and the CHOP Autism Case-Control (ACC). These pre-existing mtDNA SNP data were generated by Illumina chip analysis. We deduced the mtDNA haplogroups for all samples and utilized cases and controls that harbored European haplogroups. Generalized linear modeling analysis of the AGRE cohort suggests that J mitochondrial lineage and T2 haplogroup are risk factors for ASD (J lineage: OR = 2.22, CI=1.21-4.05, p=0.0094; T2 haplogroup: OR= 1.79, CI= 1.26-2.55, p=0.0012). Congruently, in the ACC cohort we found that haplogroup T2 is strongly associated with ASD and represents a risk factor (OR=1.45, CI=1.04-2.03, p=0.0284). These data demonstrate that ASD risk is modified by mtDNA haplogroup thus supporting our mitochondrial bioenergetic hypothesis of ASD. Grant Funding Source: Supported by Simons Foundation Autism Research Initiative and National Institutes of Health