Premium
A mitochondrial bioenergetic hypothesis for autism spectrum disorder (570.3)
Author(s) -
Chalkia Dimitra,
Derbeneva Olga,
Lvova Maria,
Lakatos Anita,
Leipzig Jeremy,
Hadley Dexter,
Hakonarson Hakon,
Wallace Douglas
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.570.3
Subject(s) - haplogroup , autism , mitochondrial dna , human mitochondrial dna haplogroup , autism spectrum disorder , genetics , haplotype , cohort , heritability of autism , biology , medicine , allele , gene , psychiatry
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