Evaluating Mitochondrial DNA Variation in Autism Spectrum Disorders

Athena Hadjixenofontos, Michael A. Schmidt, Patrice L. Whitehead, Ioanna Konidari, Dale J. Hedges, Harry H. Wright, Ruth K. Abramson, Ramkumar Menon, Scott M. Williams, Michael L. Cuccaro, Jonathan L. Haines, John R. Gilbert, Margaret A. Pericak-Vance, Eden R. Martin, Jacob L. McCauley

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Despite the increasing speculation that oxidative stress and abnormal energy metabolism may play a role in Autism Spectrum Disorders (ASD), and the observation that patients with mitochondrial defects have symptoms consistent with ASD, there are no comprehensive published studies examining the role of mitochondrial variation in autism. Therefore, we have sought to comprehensively examine the role of mitochondrial DNA (mtDNA) variation with regard to ASD risk, employing a multi-phase approach. In phase 1 of our experiment, we examined 132 mtDNA single-nucleotide polymorphisms (SNPs) genotyped as part of our genome-wide association studies of ASD. In phase 2 we genotyped the major European mitochondrial haplogroup-defining variants within an expanded set of autism probands and controls. Finally in phase 3, we resequenced the entire mtDNA in a subset of our Caucasian samples (∼400 proband-father pairs). In each phase we tested whether mitochondrial variation showed evidence of association to ASD. Despite a thorough interrogation of mtDNA variation, we found no evidence to suggest a major role for mtDNA variation in ASD susceptibility. Accordingly, while there may be attractive biological hints suggesting the role of mitochondria in ASD our data indicate that mtDNA variation is not a major contributing factor to the development of ASD.

Original languageEnglish (US)
Pages (from-to)9-21
Number of pages13
JournalAnnals of Human Genetics
Volume77
Issue number1
DOIs
StatePublished - Jan 2013

Fingerprint

Mitochondrial DNA
Autistic Disorder
Autism Spectrum Disorder
Genome-Wide Association Study
Fathers
Energy Metabolism
Single Nucleotide Polymorphism
Mitochondria
Oxidative Stress

Keywords

  • Association studies
  • Autism
  • Autism spectrum disorders
  • Genetic
  • Mitochondrial DNA

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Hadjixenofontos, A., Schmidt, M. A., Whitehead, P. L., Konidari, I., Hedges, D. J., Wright, H. H., ... McCauley, J. L. (2013). Evaluating Mitochondrial DNA Variation in Autism Spectrum Disorders. Annals of Human Genetics, 77(1), 9-21. https://doi.org/10.1111/j.1469-1809.2012.00736.x

Evaluating Mitochondrial DNA Variation in Autism Spectrum Disorders. / Hadjixenofontos, Athena; Schmidt, Michael A.; Whitehead, Patrice L.; Konidari, Ioanna; Hedges, Dale J.; Wright, Harry H.; Abramson, Ruth K.; Menon, Ramkumar; Williams, Scott M.; Cuccaro, Michael L.; Haines, Jonathan L.; Gilbert, John R.; Pericak-Vance, Margaret A.; Martin, Eden R.; McCauley, Jacob L.

In: Annals of Human Genetics, Vol. 77, No. 1, 01.2013, p. 9-21.

Research output: Contribution to journalArticle

Hadjixenofontos, A, Schmidt, MA, Whitehead, PL, Konidari, I, Hedges, DJ, Wright, HH, Abramson, RK, Menon, R, Williams, SM, Cuccaro, ML, Haines, JL, Gilbert, JR, Pericak-Vance, MA, Martin, ER & McCauley, JL 2013, 'Evaluating Mitochondrial DNA Variation in Autism Spectrum Disorders', Annals of Human Genetics, vol. 77, no. 1, pp. 9-21. https://doi.org/10.1111/j.1469-1809.2012.00736.x
Hadjixenofontos A, Schmidt MA, Whitehead PL, Konidari I, Hedges DJ, Wright HH et al. Evaluating Mitochondrial DNA Variation in Autism Spectrum Disorders. Annals of Human Genetics. 2013 Jan;77(1):9-21. https://doi.org/10.1111/j.1469-1809.2012.00736.x
Hadjixenofontos, Athena ; Schmidt, Michael A. ; Whitehead, Patrice L. ; Konidari, Ioanna ; Hedges, Dale J. ; Wright, Harry H. ; Abramson, Ruth K. ; Menon, Ramkumar ; Williams, Scott M. ; Cuccaro, Michael L. ; Haines, Jonathan L. ; Gilbert, John R. ; Pericak-Vance, Margaret A. ; Martin, Eden R. ; McCauley, Jacob L. / Evaluating Mitochondrial DNA Variation in Autism Spectrum Disorders. In: Annals of Human Genetics. 2013 ; Vol. 77, No. 1. pp. 9-21.
@article{09c2149abe0840999397c74f76244834,
title = "Evaluating Mitochondrial DNA Variation in Autism Spectrum Disorders",
abstract = "Despite the increasing speculation that oxidative stress and abnormal energy metabolism may play a role in Autism Spectrum Disorders (ASD), and the observation that patients with mitochondrial defects have symptoms consistent with ASD, there are no comprehensive published studies examining the role of mitochondrial variation in autism. Therefore, we have sought to comprehensively examine the role of mitochondrial DNA (mtDNA) variation with regard to ASD risk, employing a multi-phase approach. In phase 1 of our experiment, we examined 132 mtDNA single-nucleotide polymorphisms (SNPs) genotyped as part of our genome-wide association studies of ASD. In phase 2 we genotyped the major European mitochondrial haplogroup-defining variants within an expanded set of autism probands and controls. Finally in phase 3, we resequenced the entire mtDNA in a subset of our Caucasian samples (∼400 proband-father pairs). In each phase we tested whether mitochondrial variation showed evidence of association to ASD. Despite a thorough interrogation of mtDNA variation, we found no evidence to suggest a major role for mtDNA variation in ASD susceptibility. Accordingly, while there may be attractive biological hints suggesting the role of mitochondria in ASD our data indicate that mtDNA variation is not a major contributing factor to the development of ASD.",
keywords = "Association studies, Autism, Autism spectrum disorders, Genetic, Mitochondrial DNA",
author = "Athena Hadjixenofontos and Schmidt, {Michael A.} and Whitehead, {Patrice L.} and Ioanna Konidari and Hedges, {Dale J.} and Wright, {Harry H.} and Abramson, {Ruth K.} and Ramkumar Menon and Williams, {Scott M.} and Cuccaro, {Michael L.} and Haines, {Jonathan L.} and Gilbert, {John R.} and Pericak-Vance, {Margaret A.} and Martin, {Eden R.} and McCauley, {Jacob L.}",
year = "2013",
month = "1",
doi = "10.1111/j.1469-1809.2012.00736.x",
language = "English (US)",
volume = "77",
pages = "9--21",
journal = "Annals of Human Genetics",
issn = "0003-4800",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Evaluating Mitochondrial DNA Variation in Autism Spectrum Disorders

AU - Hadjixenofontos, Athena

AU - Schmidt, Michael A.

AU - Whitehead, Patrice L.

AU - Konidari, Ioanna

AU - Hedges, Dale J.

AU - Wright, Harry H.

AU - Abramson, Ruth K.

AU - Menon, Ramkumar

AU - Williams, Scott M.

AU - Cuccaro, Michael L.

AU - Haines, Jonathan L.

AU - Gilbert, John R.

AU - Pericak-Vance, Margaret A.

AU - Martin, Eden R.

AU - McCauley, Jacob L.

PY - 2013/1

Y1 - 2013/1

N2 - Despite the increasing speculation that oxidative stress and abnormal energy metabolism may play a role in Autism Spectrum Disorders (ASD), and the observation that patients with mitochondrial defects have symptoms consistent with ASD, there are no comprehensive published studies examining the role of mitochondrial variation in autism. Therefore, we have sought to comprehensively examine the role of mitochondrial DNA (mtDNA) variation with regard to ASD risk, employing a multi-phase approach. In phase 1 of our experiment, we examined 132 mtDNA single-nucleotide polymorphisms (SNPs) genotyped as part of our genome-wide association studies of ASD. In phase 2 we genotyped the major European mitochondrial haplogroup-defining variants within an expanded set of autism probands and controls. Finally in phase 3, we resequenced the entire mtDNA in a subset of our Caucasian samples (∼400 proband-father pairs). In each phase we tested whether mitochondrial variation showed evidence of association to ASD. Despite a thorough interrogation of mtDNA variation, we found no evidence to suggest a major role for mtDNA variation in ASD susceptibility. Accordingly, while there may be attractive biological hints suggesting the role of mitochondria in ASD our data indicate that mtDNA variation is not a major contributing factor to the development of ASD.

AB - Despite the increasing speculation that oxidative stress and abnormal energy metabolism may play a role in Autism Spectrum Disorders (ASD), and the observation that patients with mitochondrial defects have symptoms consistent with ASD, there are no comprehensive published studies examining the role of mitochondrial variation in autism. Therefore, we have sought to comprehensively examine the role of mitochondrial DNA (mtDNA) variation with regard to ASD risk, employing a multi-phase approach. In phase 1 of our experiment, we examined 132 mtDNA single-nucleotide polymorphisms (SNPs) genotyped as part of our genome-wide association studies of ASD. In phase 2 we genotyped the major European mitochondrial haplogroup-defining variants within an expanded set of autism probands and controls. Finally in phase 3, we resequenced the entire mtDNA in a subset of our Caucasian samples (∼400 proband-father pairs). In each phase we tested whether mitochondrial variation showed evidence of association to ASD. Despite a thorough interrogation of mtDNA variation, we found no evidence to suggest a major role for mtDNA variation in ASD susceptibility. Accordingly, while there may be attractive biological hints suggesting the role of mitochondria in ASD our data indicate that mtDNA variation is not a major contributing factor to the development of ASD.

KW - Association studies

KW - Autism

KW - Autism spectrum disorders

KW - Genetic

KW - Mitochondrial DNA

UR - http://www.scopus.com/inward/record.url?scp=84871618183&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84871618183&partnerID=8YFLogxK

U2 - 10.1111/j.1469-1809.2012.00736.x

DO - 10.1111/j.1469-1809.2012.00736.x

M3 - Article

VL - 77

SP - 9

EP - 21

JO - Annals of Human Genetics

JF - Annals of Human Genetics

SN - 0003-4800

IS - 1

ER -