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JAMA Psychiatry. 2017 Nov 1;74(11):1161-1168. doi: 10.1001/jamapsychiatry.2017.2604.

Association Between Mitochondrial DNA Haplogroup Variation and Autism Spectrum Disorders.

Author information

1
Center for Mitochondrial and Epigenomic Medicine, Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania.
2
Center for Systems Biomedicine, Division of Digestive Diseases, School of Medicine, University of California, Los Angeles.
3
Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania.
4
Institute of Memory Impairments and Neurological Disorders, Department of Neurobiology and Behavior, University of California, Irvine.
5
Center for Applied Genomics, Department of Pediatrics, Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania.
6
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia.

Abstract

Importance:

Autism spectrum disorders (ASD) are characterized by impairments in social interaction, communication, and repetitive or restrictive behavior. Although multiple physiologic and biochemical studies have reported defects in mitochondrial oxidative phosphorylation in patients with ASD, the role of mitochondrial DNA (mtDNA) variation has remained relatively unexplored.

Objective:

To assess what impact mitochondrial lineages encompassing ancient mtDNA functional polymorphisms, termed haplogroups, have on ASD risk.

Design, Setting, and Participants:

In this cohort study, individuals with autism and their families were studied using the Autism Genetic Resource Exchange cohort genome-wide association studies data previously generated at the Children's Hospital of Philadelphia. From October 2010 to January 2017, we analyzed the data and used the mtDNA single-nucleotide polymorphisms interrogated by the Illumina HumanHap 550 chip to determine the mtDNA haplogroups of the individuals. Taking into account the familial structure of the Autism Genetic Resource Exchange data, we then determined whether the mtDNA haplogroups correlate with ASD risk.

Main Outcomes and Measures:

Odds ratios of mitochondrial haplogroup as predictors of ASD risk.

Results:

Of 1624 patients with autism included in this study, 1299 were boys (80%) and 325 were girls (20%). Families in the Autism Genetic Resource Exchange collection (933 families, encompassing 4041 individuals: 1624 patients with ASD and 2417 healthy parents and siblings) had been previously recruited in the United States with no restrictions on age, sex, race/ethnicity, or socioeconomic status. Relative to the most common European haplogroup HHV, European haplogroups I, J, K, O-X, T, and U were associated with increased risk of ASD, as were Asian and Native American haplogroups A and M, with odds ratios ranging from 1.55 (95% CI, 1.16-2.06) to 2.18 (95% CI, 1.59-3) (adjusted P < .04). Hence, mtDNA haplogroup variation is an important risk factor for ASD.

Conclusions and Relevance:

Because haplogroups I, J, K, O-X, T, and U encompass 55% of the European population, mtDNA lineages must make a significant contribution to overall ASD risk.

PMID:
28832883
PMCID:
PMC5710217
[Available on 2018-08-23]
DOI:
10.1001/jamapsychiatry.2017.2604
[Indexed for MEDLINE]

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