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Autism Appears Overrepresented in Certain Mitochondrial Haplogroups

NEW YORK (GenomeWeb) – Autism spectrum disorder (ASD) appears to be overrepresented in some mitochondrial haplogroups, consistent with functional mitochondrial contributions to the condition.

Building from past studies describing shifts in mitochondrial metabolism in some individuals with ASD, investigators from the Children's Hospital of Philadelphia, the University of Pennsylvania, and the University of California did array-based mtDNA variant profiling on more than 1,600 children with ASD and thousands of their unaffected parents and siblings. The team's results, published in JAMA Psychiatry today, indicate that ASD does seem to be over-represented among individuals from specific mitochondrial haplotypes that circulate in European, Asian, and Native American populations.

"Our findings show that differences in mitochondrial function are important in ASD," senior author Douglas Wallace, director of CHOP's center for mitochondrial and epigenomic medicine, said in a statement. "A person's vulnerability to ASD varies according to their ancient mitochondrial lineage."

Along with the copy number variants, SNPs, and other nuclear and mitochondrial variants that have already been implicated in ASD, the team reasoned that it might be possible to pick up ancestral haplogroups with ties to the condition, since these sets of mtDNA variants reflect past population adaptations to specific environments.

"The various mtDNA haplogroup lineages arose and radiated within regional indigenous populations and are functionally different," the authors wrote, explaining that "our objective was to determine whether inherited mtDNA variation contributes to ASD risk."

As an offshoot from a broader genome-wide association study involving ASD-affected children and their family members, enrolled through the Autism Genetic Resource Exchange, the researchers used Illumina HumanHap 550 arrays to assess mtDNA SNP patterns in 1,299 boys and 325 girls with ASD from 933 families, along with 2,417 unaffected parents and siblings.

When they compared mtDNA variant profiles and corresponding haplotypes from individuals with or without ASD, the researchers found that individuals with ASD often belonged to the I, J, K, O-X, T, and U haplogroups, which together make up more than half of the haplogroups present in European populations. Similarly, ASD was overrepresented in two of the haplogroups that typically turn up in Asian and Native American populations.

"Our linkage of mtDNA haplogroups to ASD supports the hypothesis that mitochondrial functional variation is important in the causes of ASD," the authors wrote, noting that "familial predisposition to ASD based on mtDNA background haplogroup may provide [one] explanation for why high-impact CNVs do not consistently correlate with the development of ASD among siblings."