Association of mitochondrial DNA content, heteroplasmies and inter-generational transmission with autism.

Autism Spectrum Disorder / genetics Autistic Disorder / genetics DNA, Mitochondrial / genetics Female Humans Infant, Newborn Male Mitochondria / genetics Prospective Studies

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
01 07 2022
Historique:
received: 26 08 2021
accepted: 19 05 2022
entrez: 1 7 2022
pubmed: 2 7 2022
medline: 8 7 2022
Statut: epublish

Résumé

Mitochondria are essential for brain development. While previous studies linked dysfunctional mitochondria with autism spectrum disorder (ASD), the role of the mitochondrial genome (mtDNA) in ASD risk is largely unexplored. This study investigates the association of mtDNA heteroplasmies (co-existence of mutated and unmutated mtDNA) and content with ASD, as well as its inter-generational transmission and sex differences among two independent samples: a family-based study (n = 1,938 families with parents, probands and sibling controls) and a prospective birth cohort (n = 997 mother-child pairs). In both samples, predicted pathogenic (PP) heteroplasmies in children are associated with ASD risk (Meta-OR = 1.56, P = 0.00068). Inter-generational transmission of mtDNA reveals attenuated effects of purifying selection on maternal heteroplasmies in children with ASD relative to controls, particularly among males. Among children with ASD and PP heteroplasmies, increased mtDNA content shows benefits for cognition, communication, and behaviors (P ≤ 0.02). These results underscore the value of exploring maternal and newborn mtDNA in ASD.

Identifiants

DOI: 10.1038/s41467-022-30805-7 PMID: 35778412 PMC: PMC9249801
pubmed: 35778412
doi: 10.1038/s41467-022-30805-7
pii: 10.1038/s41467-022-30805-7
pmc: PMC9249801
doi:

Substances chimiques

DNA, Mitochondrial 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

3790

Subventions

Organisme : NICHD NIH HHS
ID : R01 HD086013
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD041702
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD098232
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES031272
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES031521
Pays : United States

Informations de copyright

© 2022. The Author(s).

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Auteurs

Yiqin Wang (Y)

Division of Nutritional Sciences, Cornell University, Ithaca, NY, USA.
ORCID: 0000-0003-4714-774X

Xiaoxian Guo (X)

Division of Nutritional Sciences, Cornell University, Ithaca, NY, USA.

Xiumei Hong (X)

Center on Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.

Guoying Wang (G)

Center on Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.

Colleen Pearson (C)

Department of Pediatrics, Boston University School of Medicine and Boston Medical Center, Boston, MA, USA.

Barry Zuckerman (B)

Department of Pediatrics, Boston University School of Medicine and Boston Medical Center, Boston, MA, USA.

Andrew G Clark (AG)

Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA.
Department of Computational Biology, Cornell University, Ithaca, NY, USA.
ORCID: 0000-0001-7159-8511

Kimberly O O'Brien (KO)

Division of Nutritional Sciences, Cornell University, Ithaca, NY, USA.
ORCID: 0000-0002-0954-1706

Xiaobin Wang (X)

Center on Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA. xwang82@jhu.edu.
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA. xwang82@jhu.edu.
ORCID: 0000-0003-4451-302X

Zhenglong Gu (Z)

Division of Nutritional Sciences, Cornell University, Ithaca, NY, USA. zg27@cornell.edu.
Center for Mitochondrial Genetics and Medicine, Greater Bay Area Institute of Precision Medicine (Guangzhou), Fudan University, Guangzhou, China. zg27@cornell.edu.
ORCID: 0000-0002-7733-432X

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Classifications MeSH

questionsmedicales.fr › Troubles mentaux › Troubles du développement neurologique › Troubles généralisés du développement de l'enfant › Trouble du spectre autistique › Association of mitochondrial DNA content,...
questionsmedicales.fr › Troubles mentaux › Troubles du développement neurologique › Troubles généralisés du développement de l'enfant › Trouble du spectre autistique › Trouble autistique › Association of mitochondrial DNA content,...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ADN › ADN mitochondrial › Association of mitochondrial DNA content,...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Association of mitochondrial DNA content,...
questionsmedicales.fr › Personnes › Tranches d'âge › Nourrisson › Nouveau-né › Association of mitochondrial DNA content,...
questionsmedicales.fr › Cellules › Structures cellulaires › Fractions subcellulaires › Mitochondries › Association of mitochondrial DNA content,...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études prospectives › Association of mitochondrial DNA content,...